Hypothesis

414 Matching Annotations

Oct 2026
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

Molecular and clinical profile of VWD in a large cohort of Chinese population: application of next generation sequencing and CNVplex ® technique

13
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Case: P64, Chinese, female, 2yo
 
 DiseaseAssertion: VWD3
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type O blood, bleeding score = 7; VWF:Ag (%) = 1.3, VWF:RCo (%) = 1.1, FVIII:C (%) = 4.0, VWF:CB (%) = 1.5, VWFpp (%) = 0.9, VWF:RCo/VWF:Ag = 0.8, VWF:CB/VWF:Ag = 1.2, VWFpp/VWF:Ag = 0.7, FVIII:C/VWF:Ag = 3.1
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant: c.196C>T (p.Gln66Ter)
 
 HGVS: NM_000552.5:c.196C>T (p.Gln66Ter)
 
 ClinVarID: NA
 
 CAID: CA383507653; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383507653
 
 gnomAD: absent
 
 Variant 2: c.4457C>A (p.Ser1486Ter)
 
 HGVS: NM_000552.5:c.4457C>A (p.Ser1486Ter)
 
 ClinVarID: NA
 
 CAID: CA383501822; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383501822
 
 gnomAD: absent
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD3 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Nonsense CAid:CA383507653 CAid:CA383501822 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
2. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Case: P49, Chinese, male, 7yo
 
 DiseaseAssertion: VWD3
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type B blood, bleeding score = 3; VWF:Ag (%) = 1.5, VWF:RCo (%) = 1.3, FVIII:C (%) = 8.0, VWF:CB (%) = 1.6, VWFpp (%) = 1.1, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 1.1, VWFpp/VWF:Ag = 0.7, FVIII:C/VWF:Ag = 5.3
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.1534-13_c.1551delinsCA - unregistered variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Variant 2: c.2968-14A>G
 
 HGVS: NM_000552.5:c.2968-14A>G
 
 ClinVarID: NA
 
 CAID: CA690485152; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA690485152
 
 gnomAD: absent
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD3 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Regulatory UnregisteredVariant CAid:CA690485152 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
3. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Case: P15, Chinese, female, 52yo
 
 DiseaseAssertion: VWD3
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type A blood, bleeding score = 15; VWF:Ag (%) = 1.5, VWF:RCo (%) = 1.6, FVIII:C (%) = 7.1, VWF:CB (%) = 1.1, VWFpp (%) = 1.2, VWF:RCo/VWF:Ag = 1.1, VWF:CB/VWF:Ag = 0.7, VWFpp/VWF:Ag = 0.8, FVIII:C/VWF:Ag = 4.7
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.813C>A (p.Tyr271Ter)
 
 HGVS: NM_000552.5:c.813C>A (p.Tyr271Ter)
 
 ClinVarID: NA
 
 CAID: CA383508534; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383508534
 
 gnomAD: absent
 
 Variant 2: c.893dup (p.Met299fs)
 
 HGVS: NM_000552.4(VWF):c.893dup (p.Met299fs)
 
 ClinVarID: 100511; https://www.ncbi.nlm.nih.gov/clinvar/variation/100511/
 
 CAID: NA
 
 gnomAD: absent
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD3 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Nonsense Mutation:Frameshift CAid:CA383508534 ClinVarID:100511 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
4. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Case: P80, Chinese, female, 1yo
 
 DiseaseAssertion: VWD3
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type B blood, bleeding score = 6; VWF:Ag (%) = 0.8, VWF:RCo (%) = 1.0, FVIII:C (%) = 3.0, VWF:CB (%) = 0.7, VWFpp (%) = 0.6, VWF:RCo/VWF:Ag = 1.3, VWF:CB/VWF:Ag = 0.9, VWFpp/VWF:Ag = 0.8, FVIII:C/VWF:Ag = 3.8
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.4725delG - Unregistered Variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Variant 2: c.6099C>G (p.Tyr2033Ter)
 
 HGVS: NM_000552.5:c.6099C>G (p.Tyr2033Ter)
 
 ClinVarID: NA
 
 CAID: CA383492399; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383492399
 
 gnomAD: absent
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD3 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Frameshift Mutation:Nonsense UnregisteredVariant CAid:CA383492399 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
5. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Case: P57, Chinese, male, 28yo
 
 DiseaseAssertion: VWD2B
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type AB blood, bleeding score = 5; VWF:Ag (%) = 33.4, VWF:RCo (%) = 3.2, FVIII:C (%) = 49.2, VWF:CB (%) = 4.8, VWFpp (%) = 67.3, VWF:RCo/VWF:Ag = 0.1, VWF:CB/VWF:Ag = 0.1, VWFpp/VWF:Ag = 2.0, FVIII:C/VWF:Ag = 1.5, RIPA (0.5 mg/ml, %) = 18.2, PLT(×109/l) = 146
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.2089G>C (p.Glu697Gln)
 
 HGVS: NM_000552.5:c.2089G>C (p.Glu697Gln)
 
 ClinVarID: NA
 
 CAID: CA383494704; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383494704
 
 gnomAD: absent
 
 Variant 2: c.3922C>T (p.Arg1308Cys)
 
 HGVS: NM_000552.4(VWF):c.3922C>T (p.Arg1308Cys)
 
 ClinVarID: 289; https://www.ncbi.nlm.nih.gov/clinvar/variation/289/
 
 CAID: NA
 
 gnomAD: absent
 
 Variant 3: c.8113G>A (p.Gly2705Arg)
 
 HGVS: NM_000552.4(VWF):c.8113G>A (p.Gly2705Arg)
 
 ClinVarID: 256702; https://www.ncbi.nlm.nih.gov/clinvar/variation/256702/
 
 CAID: NA
 
 gnomAD: MAF = 0.1254 (3839/30614 alleles; 279 homozygotes)
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD2B Mutation:Missense Zygosity:CompoundHeterozygous InheritancePattern:AutosomalRecessive CAid:CA383494704 ClinVarID:289 ClinVarID:256702 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
6. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Case: P88, Chinese, female, 4yo
 
 DiseaseAssertion: VWD3
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type O blood, bleeding score = 11; VWF:Ag (%) = 0.5, VWF:RCo (%) = <0.5, FVIII:C (%) = 3.0, VWF:CB (%) = <0.5, VWFpp (%) = <0.5, VWF:RCo/VWF:Ag = NA, VWF:CB/VWF:Ag = NA, VWFpp/VWF:Ag = NA, FVIII:C/VWF:Ag = 6.0
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant: 1 c.1591C>T (p.Gln531Ter)
 
 HGVS: NM_000552.5:c.1591C>T (p.Gln531Ter)
 
 ClinVarID: NA
 
 CAID: CA383498290; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383498290
 
 gnomAD: absent
 
 Variant 2: c.6678dupC - Unregistered Variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD3 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Nonsense Mutation:Frameshift CAid:CA383498290 UnregisteredVariant inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
7. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Case: P43, Chinese, male, 7yo
 
 DiseaseAssertion: VWD2N
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type B blood, bleeding score = 3; VWF:Ag (%) = 48.8, VWF:RCo (%) = 49.9, FVIII:C (%) = 6.4, VWF:CB (%) = 63.9, VWFpp (%) = 52.4, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 1.3, VWFpp/VWF:Ag = 1.1, FVIII:C/VWF:Ag = 0.1, VWF: FVIIIB (%) = 0.0
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.2372C>T (p.Thr791Met)
 
 HGVS: NM_000552.4(VWF):c.2372C>T (p.Thr791Met)
 
 ClinVarID: 294; https://www.ncbi.nlm.nih.gov/clinvar/variation/294/
 
 CAID: NA
 
 gnomAD: MAF = 0.00003984 (1/25100 alleles) in European (Finnish) population; https://gnomad.broadinstitute.org/variant/12-6153527-G-A?dataset=gnomad_r2_1
 
 Variant 2: c.2574C>G (p.Cys858Trp)
 
 HGVS: NM_000552.5:c.2574C>G (p.Cys858Trp)
 
 ClinVarID: NA
 
 CAID: CA232299278; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA232299278
 
 gnomAD: MAF = 0.0001002 (2/19954 alleles) in the East Asian population; https://gnomad.broadinstitute.org/variant/12-6143965-G-C
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD2N InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Missense ClinVarID:294 CAid:CA232299278 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
8. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Case: P90, Chinese, female, 30yo
 
 DiseaseAssertion: VWD2A
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type O blood, bleeding score = 12; VWF:Ag (%) = 10.1, VWF:RCo (%) = 3.3, FVIII:C (%) = 10.7, VWF:CB (%) = 2.6, VWFpp (%) = 151.7, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 0.3, VWFpp/VWF:Ag = 15.0, FVIII:C/VWF:Ag = 1.1
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.1730-2A>G
 
 HGVS: NM_000552.4(VWF):c.1730-2A>G
 
 ClinVarID: 100189; https://www.ncbi.nlm.nih.gov/clinvar/variation/100189/
 
 CAID: NA
 
 gnomAD: absent
 
 Variant 2: c.6979T>A (p.Cys2327Ser)
 
 HGVS: NM_000552.3:c.6979T>A (p.Cys2327Ser)
 
 ClinVarID: NA
 
 CAID: CA383492042; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383492042
 
 gnomAD: absent
 
 Individual CaseInfo Gene:VWF InheritancePattern:AutosomalRecessive DiseaseEntity:VWD2A Mutation:Regulatory Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:100189 CAid:CA383492042 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
9. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Case: P38, Chinese, female, 14yo
 
 DiseaseAssertion: VWD3
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type O blood, bleeding score = 9; VWF:Ag (%) = 1.3, VWF:RCo (%) = 1.0, FVIII:C (%) = 4.5, VWF:CB (%) = 0.7, VWFpp (%) = 0.8, VWF:RCo/VWF:Ag = 0.8, VWF:CB/VWF:Ag = 0.5, VWFpp/VWF:Ag = 0.6, FVIII:C/VWF:Ag = 3.5
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.2684A>G (p.Gln895Arg)
 
 HGVS: NM_000552.5:c.2684A>G (p.Gln895Arg)
 
 ClinVarID: NA
 
 CAID: CA383519914; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383519914
 
 gnomAD: NA
 
 Variant 2: c.3043G>T (p.Glu1015Ter)
 
 HGVS: NM_000552.5:c.3043G>T (p.Glu1015Ter)
 
 ClinVarID: NA
 
 CAID: CA383514739; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383514739
 
 gnomAD: absent
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD3 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Missense Mutation:Nonsense CAid:CA383519914 CAid:CA383514739 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
10. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Case: P7, Chinese, female, 27yo
 
 DiseaseAssertion: VWD1
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type O blood, bleeding score = 9; VWF:Ag (%) = 5.4, VWF:RCo (%) = 5.3, FVIII:C (%) = 28, VWF:CB (%) = 4.1, VWFpp (%) = 4.8, VWF:RCo/VWF:Ag = 1.0, VWF:CB/VWF:Ag = 0.8, VWFpp/VWF:Ag = 0.9, FVIII:C/VWF:Ag = 5.2, RIPA (1.2 mg/ml, %) = 73.3
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.711C>G (p.Cys237Trp)
 
 HGVS: NM_000552.3:c.711C>G (p.Cys237Trp)
 
 ClinVarID: NA
 
 CAID: CA383509260; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383509260
 
 gnomAD: absent
 
 Variant: c.1109+47T>A - Unregistered Variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Individual CaseInfo Gene:VWF InheritancePattern:AutosomalRecessive DiseaseEntity:VWD1 Mutation:Missense Mutation:Regulatory Zygosity:CompoundHeterozygous CAid:CA383509260 UnregisteredVariant inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
11. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Case: P10, Chinese, male, 5yo
 
 DiseaseAssertion: VWD1
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type A blood, bleeding score = 2; VWF:Ag (%) = 4.2, VWF:RCo (%) = 3.8, FVIII:C (%) = 30.1, VWF:CB (%) = 3.5, VWFpp (%) = 4.1, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.8, VWFpp/VWF:Ag = 1.0, FVIII:C/VWF:Ag = 7.4, RIPA (1.2 mg/ml, %) = 40.1
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.7199delA (p.Asn2400Thrfs*4) - Unregistered Variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Variant 2: c.8155+5G>C - Unregistered Variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Individual CaseInfo Gene:VWF InheritancePattern:AutosomalRecessive DiseaseEntity:VWD1 Mutation:Frameshift Mutation:Regulatory Zygosity:CompoundHeterozygous UnregisteredVariant inferred_gene_hgnc:12726 inferred_gene_source:Gene_Name ClinGen VWF
12. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Case: P77, Chinese, female, 10yo
 
 DiseaseAssertion: VWD3
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type B blood, bleeding score = 7; VWF:Ag (%) = 3.0, VWF:RCo (%) = 2.7, FVIII:C (%) = 6.8, VWF:CB (%) = 2.1, VWFpp (%) = 3.2, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.7, VWFpp/VWF:Ag = 1.1, FVIII:C/VWF:Ag = 2.3
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.6771C>A (p.Cys2257Ter)
 
 HGVS: NM_000552.5:c.6771C>A (p.Cys2257Ter)
 
 ClinVarID: NA
 
 CAID: CA383489897; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383489897
 
 gnomAD: absent
 
 Variant 2: c.8116-2delA - unregistered variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD3 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Nonsense Mutation:Regulatory CAid:CA383489897 UnregisteredVariant inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
13. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Case: P27, Chinese, female, 3yo
 
 DiseaseAssertion: VWD2N
 
 FamilyInfo: NA
 
 ParentalGenotype(s): NA
 
 CasePresentingHPOs: HP:0012147
 
 (Reduced quantity of VWF)
 
 CaseHPOFreeText: type B blood, bleeding score = 6; VWF:Ag (%) = 9.5, VWF:RCo (%) = 8.9, FVIII:C (%) = 6.5, VWF:CB (%) = 6.9, VWFpp (%) = 10.8, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.7, VWFpp/VWF:Ag = 1.1, FVIII:C/VWF:Ag = 0.7, VWF: FVIIIB (%) = 0.0
 
 CaseNOTHPOs:
 
 CaseNOTHPOFreeText:
 
 CasePreviousTesting: NA
 
 GenotypingMethod: NGS
 
 PreviouslyPublished: NA
 
 Gene: VWF
 
 Variant 1: c.2396G>A (p.Cys799Tyr)
 
 HGVS: NM_000552.5:c.2396G>A (p.Cys799Tyr)
 
 ClinVarID: NA
 
 CAID: CA232300402; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA232300402
 
 gnomAD: absent
 
 Variant 2: c.3197_3201del - unregistered variant
 
 HGVS: NA
 
 ClinVarID: NA
 
 CAID: NA
 
 gnomAD: NA
 
 Individual CaseInfo Gene:VWF DiseaseEntity:VWD2N InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Missense UnregisteredVariant Mutation:Frameshift CAid:CA232300402 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
Visit annotations in context

Tags

DiseaseEntity:VWD3

CAid:CA383492399

DiseaseEntity:VWD2B

CAid:CA383507653

DiseaseEntity:VWD1

UnregisteredVariant

CaseInfo

CAid:CA383508534

Mutation:Missense

Individual

ClinVarID:100189

CAid:CA232299278

CAid:CA383519914

ClinVarID:294

ClinVarID:100511

CAid:CA383494704

ClinVarID:256702

CAid:CA383492042

CAid:CA383498290

CAid:CA232300402

inferred_gene_source:CAID

DiseaseEntity:VWD2N

CAid:CA383514739

Mutation:Nonsense

ClinGen VWF

Mutation:Regulatory

ClinVarID:289

Zygosity:CompoundHeterozygous

CAid:CA383489897

CAid:CA690485152

CAid:CA383501822

InheritancePattern:AutosomalRecessive

inferred_gene_source:Gene_Name

DiseaseEntity:VWD2A

CAid:CA383509260

inferred_gene_hgnc:12726

Mutation:Frameshift

Gene:VWF

Annotators

ClingenBaseline

URL

pubmed.ncbi.nlm.nih.gov/28536718/
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Clinical, Phenotypic and Genotypic Characteristics of Von Willebrand Disease in Afro-Caribbeans: Results From a Study in Martinique Island, French West Indies

25
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  41 S
  
  Case: Patient 41, Family S (Table 1.), M/63, Afro-Caribbean
  
  DiseaseAssertion: Indeterminant
  
  FamilyInfo: Patient 39 (F/76, Afro-Caribbean), Patient 40 (F/38, Afro-Caribbean)and Patient 52 (F/48, Afro Caribbean) also from Family S. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 0, FVIII:C (IU/dL) = 100, VWF:Ag (IU/dL) = 92, VWF:Act (IU/dL) = 36
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.4138A > G, p.(Ile1380Val)
  
  HGVS: NM_000552.5:c.4138A>G (p.Ile1380Val)
  
  ClinVarID: 310063
  
  CAID: CA6402595
  
  gnomAD: MAF of 0.1184 (8878/74958 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019280-T-C?dataset=gnomad_r4
  
  Variant: c.4304A > G, p.(Asn1435Ser)
  
  HGVS: NM_000552.5:c.4304A>G (p.Asn1435Ser)
  
  ClinVarID: 310062
  
  CAID: CA6402552
  
  gnomAD: MAF of 0.1124 (8427/74964 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019114-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.4628C > G p.(Ser1543Cys)
  
  HGVS: NM_000552.5:c.4628C>G (p.Ser1543Cys)
  
  ClinVarID: 4533008
  
  CAID: CA383500651
  
  gnomAD:
  
  Individual CaseInfo FamilyInfo Gene:VWF Zygosity:CompoundHeterozygous ClinVarID:310063 CAID:CA6402595 ClinVarID:310062 CAID:CA6402552 ClinVarID:256679 CAID:CA6402534 ClinVarID:4533008 CAID:CA383500651 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
2. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  28 F
  
  Case: Patient 28, Family F (Table 1.), F/55, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 8 (M/86, Afro-Caribbean) and Patient 9 (F/76, Afro-Caribbean) also from Family F. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 6, FVIII:C (IU/dL) = 112, VWF:Ag (IU/dL) = 10, VWF:Act (IU/dL) = 14
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group A+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3426T > C, p.(Cys1142 =)
  
  HGVS: NM_000552.5:c.3426T>C (p.Cys1142=)
  
  ClinVarID: 256668
  
  CAID: CA6402757
  
  gnomAD: MAF of 0.2077 (7935/38206 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022852-A-G?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.3485C > T, p.(Pro1162Leu)
  
  HGVS: NM_000552.5:c.3485C>T (p.Pro1162Leu)
  
  ClinVarID: 256669
  
  CAID: CA6402756
  
  gnomAD: MAF of 0.2076 (7087/34136 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022793-G-A?dataset=gnomad_r4
  
  Variant: c.3486A > G, p.(Pro1162 =)
  
  HGVS: NM_000552.5:c.3486A>G (p.Pro1162=)
  
  ClinVarID: 256670
  
  CAID: CA6402755
  
  gnomAD: MAF of 0.2083 (7074/33968 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022792-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous Zygosity:Homozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:256668 CAID:CA6402757 ClinVarID:309 CAID:CA228410 ClinVarID:256669 CAID:CA6402756 ClinVarID:256670 CAID:CA6402755 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline FamilyInfo inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
3. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  38 R
  
  Case: Patient 38, Family R (Table 1.), F/51, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 36 (M/22, Afro-Caribbean) and Patient 37 (M/20, Afro-Caribbean) also from Family R. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 6, FVIII:C (IU/dL) = 30, VWF:Ag (IU/dL) = 20, VWF:Act (IU/dL) = 14
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo Zygosity:CompoundHeterozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
4. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  52 S
  
  Case: Patient 52, Family S (Table 1.), F/48, Afro-Caribbean
  
  DiseaseAssertion: VWD1
  
  FamilyInfo: Patient 39 (F/76, Afro-Caribbean), Patient 40 (F/38, Afro-Caribbean)and Patient 41 (m/63, Afro Caribbean) also from Family S. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 4, FVIII:C (IU/dL) = NA, VWF:Ag (IU/dL) = 30, VWF:Act (IU/dL) = 30
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: deletion of exons 9-10
  
  HGVS: NM_000552.5:c.1030_1317del (p.Gly344_Arg439del)
  
  ClinVarID:
  
  CAID: CA3260663889
  
  gnomAD:
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Individual CaseInfo FamilyInfo Gene:VWF Zygosity:CompoundHeterozygous CAID:CA3260663889 ClinVarID:256679 CAID:CA6402534 AlleleOrigin:Germline DiseaseEntity:VWD1 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
5. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  5 B
  
  Case: Patient 5, Family B (Table 1.), F/47, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 3 (M/30, Afro-Caribbean) from same family. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 7, FVIII:C (IU/dL) = 30, VWF:Ag (IU/dL) = 15, VWF:Act (IU/dL) = 17
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O-
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF FamilyInfo Zygosity:CompoundHeterozygous DiseaseEntity:VWD2A CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
6. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  26 N
  
  Case: Patient 26, Family N (Table 1.), F/58, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 27 (M/20, Afro-Caribbean) also in Family N. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =12, FVIII:C (IU/dL) = NA, VWF:Ag (IU/dL) = 15, VWF:Act (IU/dL) = 10
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group B+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =)
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline FamilyInfo inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
7. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  17 G
  
  Case: Patient 17, Family G (Table 1.), F/79, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 10 (M/22, Afro-Caribbean) and Patient 17 (F/58, Afro-Caribbean) also from Family G. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =4, FVIII:C (IU/dL) = 29, VWF:Ag (IU/dL) = 17, VWF:Act (IU/dL) = 5
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group A+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo Zygosity:CompoundHeterozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
8. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  16 G
  
  Case: Patient 16, Family G (Table 1.), F/58, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 10 (M/22, Afro-Caribbean) and Patient 17 (F/79, Afro-Caribbean) also from Family G. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =23, FVIII:C (IU/dL) = 44, VWF:Ag (IU/dL) = 20, VWF:Act (IU/dL) = 14
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group A+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo Zygosity:CompoundHeterozygous AlleleOrigin:Germline CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
9. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  19 L
  
  Case: Patient 19, Family L (Table 1.), M/76, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo:
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =4, FVIII:C (IU/dL) = NA, VWF:Ag (IU/dL) = 70, VWF:Act (IU/dL) = 28
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group A+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF Zygosity:CompoundHeterozygous Zygosity:Homozygous DiseaseEntity:VWD2A CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
10. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  13 I
  
  Case: Patient 13, Family I (Table 1.), F/65, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 21 (F/97, Afro-Caribbean), Patient 22 (F/67, Afro-Caribbean), Patient 23 (F/86, Afro-Caribbean), Patient 24 (F/92, Afro-Caribbean), Patient 25 (F/62, Afro-Carribean) also from Family I. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =12, FVIII:C (IU/dL) = 18, VWF:Ag (IU/dL) = 18, VWF:Act (IU/dL) = 7
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3258C > T, p.(Tyr1086 =)
  
  HGVS: NM_000552.5:c.3258C>T (p.Tyr1086=)
  
  ClinVarID: 256664
  
  CAID: CA6402788
  
  gnomAD: MAF of 0.1284 (9131/71128 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6023752-G-A?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His) ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo Zygosity:CompoundHeterozygous AlleleOrigin:Germline CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:256664 CAID:CA6402788 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
11. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  8 F
  
  Case: Patient 8, Family F (Table 1.), M/86, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 9 (F/76, Afro-Caribbean) and Patient 28 (F/55, Afro-Caribbean) also from Family F. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 5, FVIII:C (IU/dL) = 17, VWF:Ag (IU/dL) = 20, VWF:Act (IU/dL) = 10
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3426T > C, p.(Cys1142 =)
  
  HGVS: NM_000552.5:c.3426T>C (p.Cys1142=)
  
  ClinVarID: 256668
  
  CAID: CA6402757
  
  gnomAD: MAF of 0.2077 (7935/38206 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022852-A-G?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.3485C > T, p.(Pro1162Leu)
  
  HGVS: NM_000552.5(VWF):c.3485C>T (p.Pro1162Leu)
  
  ClinVarID: 256669
  
  CAID: CA6402756
  
  gnomAD: MAF of 0.2076 (7087/34136 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022793-G-A?dataset=gnomad_r4
  
  Variant: c.3486A > G, p.(Pro1162 =)
  
  HGVS: NM_000552.5:c.3486A>G (p.Pro1162=)
  
  ClinVarID: 256670
  
  CAID: CA6402755
  
  gnomAD: MAF of 0.2083 (7074/33968 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022792-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF Zygosity:CompoundHeterozygous Zygosity:Homozygous DiseaseEntity:VWD2A FamilyInfo CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:256668 CAID:CA6402757 ClinVarID:309 CAID:CA228410 ClinVarID:256669 CAID:CA6402756 ClinVarID:256670 CAID:CA6402755 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
12. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  53 Z
  
  Case: Patient 53, Family Z (Table 1.), F/92, Afro-Caribbean
  
  DiseaseAssertion: VWD1
  
  FamilyInfo: NA
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 0, FVIII:C (IU/dL) = 33, VWF:Ag (IU/dL) = 35, VWF:Act (IU/dL) = 30
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3258C > T, p.(Tyr1086 =)
  
  HGVS: NM_000552.5:c.3258C>T (p.Tyr1086=)
  
  ClinVarID: 256664
  
  CAID: CA6402788
  
  gnomAD: MAF of 0.1284 (9131/71128 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6023752-G-A?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Variant: c.6647del, (Cys2216Phefs*9)
  
  HGVS: NM_000552.5:c.6647del (p.Cys2216Phefs*9)
  
  ClinVarID:
  
  CAID: CA2695216024
  
  gnomAD:
  
  Variant: c.6859C > T, p.(Arg2287Trp)
  
  HGVS: NM_000552.5:c.6859C>T (p.Arg2287Trp)
  
  ClinVarID: 100450
  
  CAID: CA228760
  
  gnomAD: MAF of 0.008928 (670/75044 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5985605-G-A?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD1 Zygosity:CompoundHeterozygous ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:256664 CAID:CA6402788 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 CAID:CA2695216024 ClinVarID:100450 CAID:CA228760 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
13. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  21 I
  
  Case: Patient 21, Family I (Table 1.), F/97, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 13 (F/65, Afro-Caribbean), Patient 22 (F/67, Afro-Caribbean), Patient 23 (F/86, Afro-Caribbean), Patient 24 (F/92, Afro-Caribbean), Patient 25 (F/62, Afro-Carribean) also from Family I. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =0, FVIII:C (IU/dL) = 35, VWF:Ag (IU/dL) = 25, VWF:Act (IU/dL) = 8
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group B+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3258C > T, p.(Tyr1086 =)
  
  HGVS: NM_000552.5:c.3258C>T (p.Tyr1086=)
  
  ClinVarID: 256664
  
  CAID: CA6402788
  
  gnomAD: MAF of 0.1284 (9131/71128 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6023752-G-A?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF FamilyInfo DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:256664 CAID:CA6402788 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
14. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  14 J
  
  Case: Patient 14, Family J (Table 1.), M/36, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 15 (F/64, Afro-Carribean) also from Family J. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =0, FVIII:C (IU/dL) = 25, VWF:Ag (IU/dL) = 25, VWF:Act (IU/dL) = 8
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText:
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.3505T > A, p.(Cys1169Ser)
  
  HGVS: NM_000552.5:c.3505T>A (p.Cys1169Ser)
  
  ClinVarID:
  
  CAID: CA383511219
  
  gnomAD:
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous CAID:CA383511219 ClinVarID:256679 CAID:CA6402534 FamilyInfo inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
15. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  25 I
  
  Case: Patient 25, Family I (Table 1.), F/62, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 13 (F/65, Afro-Caribbean), Patient 21 (F/97, Afro-Caribbean), Patient 22 (F/67, Afro-Caribbean), Patient 23 (F/86, Afro-Caribbean), Patient 24 (F/92, Afro-Carribean) also from Family I. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =6, FVIII:C (IU/dL) = 16, VWF:Ag (IU/dL) = 25, VWF:Act (IU/dL) = 14
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group B+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3258C > T, p.(Tyr1086 =)
  
  HGVS: NM_000552.5:c.3258C>T (p.Tyr1086=)
  
  ClinVarID: 256664
  
  CAID: CA6402788
  
  gnomAD: MAF of 0.1284 (9131/71128 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6023752-G-A?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4138A > G, p.(Ile1380Val)
  
  HGVS: NM_000552.5:c.4138A>G (p.Ile1380Val)
  
  ClinVarID: 310063
  
  CAID: CA6402595
  
  gnomAD: MAF of 0.1184 (8878/74958 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019280-T-C?dataset=gnomad_r4
  
  Variant: c.4304A > G, p.(Asn1435Ser)
  
  HGVS: NM_000552.5:c.4304A>G (p.Asn1435Ser)
  
  ClinVarID: 310062
  
  CAID: CA6402552
  
  gnomAD: MAF of 0.1124 (8427/74964 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019114-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo Zygosity:CompoundHeterozygous Zygosity:Homozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:256664 CAID:CA6402788 ClinVarID:309 CAID:CA228410 ClinVarID:310063 CAID:CA6402595 ClinVarID:310062 CAID:CA6402552 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
16. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  12 H
  
  Case: Patient 12, Family H (Table 1.), F/99, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 11 (M/71, Afro-Caribbean) also from Family H. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =8, FVIII:C (IU/dL) = 56, VWF:Ag (IU/dL) = 15, VWF:Act (IU/dL) = 24
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF FamilyInfo DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous AlleleOrigin:Germline CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
17. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  3 B
  
  Case: Patient 3, Family B (Table 1.), M/30, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 5 (F/47, Afro-Caribbean) from same family B (Table 1.).
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 4, FVIII:C (IU/dL) = 14, VWF:Ag (IU/dL) = 10, VWF:Act (IU/dL) = 4.9
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.2739A > C, p.(Gly913 =)
  
  HGVS: NM_000552.5:c.2739A>C p.(Gly913=)
  
  ClinVarID: 1336650
  
  CAID: CA6402959
  
  gnomAD: MAF of 0.003374 (253/74996 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/12-6031525-T-G?dataset=gnomad_r4
  
  Variant: c.2815G > A, p.(Gly939Arg)
  
  HGVS: NM_000552.5:c.2815G>A (p.Gly939Arg)
  
  ClinVarID: 2500546
  
  CAID: CA6402950
  
  gnomAD: MAF of 0.0009595 (72/75038 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/12-6031449-C-T?dataset=gnomad_r4
  
  Variant: c.3101_3103delCCA (p.Thr1034del)
  
  HGVS: NM_000552.5:c.3101_3103delCCA (p.Thr1034del)
  
  ClinVarID: 802812
  
  CAID: CA6402852
  
  gnomAD: MAF of 0.01532 (1150/7504 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6025910-CTGG-C?dataset=gnomad_r4
  
  Variant: c.4138A > G, p.(Ile1380Val)
  
  HGVS: NM_000552.5:c.4138A>G (p.Ile1380Val)
  
  ClinVarID: 310063
  
  CAID: CA6402595
  
  gnomAD: MAF of 0.1184 (8878/74958 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019280-T-C?dataset=gnomad_r4
  
  Variant: c.4304A > G p.(Asn1435Ser)
  
  HGVS: NM_000552.5:c.4304A>G (p.Asn1435Ser)
  
  ClinVarID: 310062
  
  CAID: CA6402552
  
  gnomAD: MAF of 0.1124 (8427/74964 alleles) in Africa/African American population https://gnomad.broadinstitute.org/variant/chr12-6019114-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF ClinVarID:1336650 CAID:CA6402959 ClinVarID:2500546 CAID:CA6402950 ClinVarID:802812 CAID:CA6402852 ClinVarID:310063 CAID:CA6402595 ClinVarID:310062 CAID:CA6402552 ClinVarID:256679 CAID:CA6402534 Zygosity:CompoundHeterozygous DiseaseEntity:VWD2A FamilyInfo inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
18. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  7 E
  
  Case: Patient 7, Family E (Table 1.), M/47, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: NA
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 1, FVIII:C (IU/dL) = 15, VWF:Ag (IU/dL) = 15, VWF:Act (IU/dL) = 11
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
19. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  6 D
  
  Case: Patient 6, Family D (Table 1.), F/60, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: NA
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 12, FVIII:C (IU/dL) = 13, VWF:Ag (IU/dL) = 10, VWF:Act (IU/dL) = 12
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3258C > T, p.(Tyr1086 =)
  
  HGVS: NM_000552.5:c.3258C>T (p.Tyr1086=)
  
  ClinVarID: 256664
  
  CAID: CA6402788
  
  gnomAD: MAF of 0.1284 (9131/71128 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6023752-G-A?dataset=gnomad_r4
  
  Variant: c.3426T > C, p.(Cys1142 =)
  
  HGVS: NM_000552.5:c.3426T>C (p.Cys1142=)
  
  ClinVarID: 256668
  
  CAID: CA6402757
  
  gnomAD: MAF of 0.2077 (7935/38206 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022852-A-G?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.3485C > T, p.(Pro1162Leu)
  
  HGVS: NM_000552.5:c.3485C>T (p.Pro1162Leu)
  
  ClinVarID: 256669
  
  CAID: CA6402756
  
  gnomAD: MAF of 0.2076 (7087/34136 alleles) African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022793-G-A?dataset=gnomad_r4
  
  Variant: c.3486A > G, p.(Pro1162 =)
  
  HGVS: NM_000552.5:c.3486A>G (p.Pro1162=)
  
  ClinVarID: 256670
  
  CAID: CA6402755
  
  gnomAD: MAF of 0.2083 (7074/33968 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022792-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous Zygosity:Homozygous CAID:CA6403368 ClinVarID:100224 CAID:CA228345 ClinVarID:256664 CAID:CA6402788 ClinVarID:256668 CAID:CA6402757 ClinVarID:309 CAID:CA228410 ClinVarID:256669 CAID:CA6402756 ClinVarID:256670 CAID:CA6402755 ClinVarID:256679 CAID:CA6402534 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
20. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  11 H
  
  Case: Patient 11, Family H (Table 1.), M/71, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 12 (F/99, Afro-Caribbean) also from Family H. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =15, FVIII:C (IU/dL) = 30, VWF:Ag (IU/dL) = 15, VWF:Act (IU/dL) = 7
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo FamilyInfo Gene:VWF DiseaseEntity:VWD2A AlleleOrigin:Germline Zygosity:CompoundHeterozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
21. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  30 O
  
  Case: Patient 30, Family O (Table 1.), M/42, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 31 (F/73, Afro-Caribbean) also from Family O. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 4, FVIII:C (IU/dL) = 35, VWF:Ag (IU/dL) = 10, VWF:Act (IU/dL) = 29
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A Zygosity:CompoundHeterozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:309 CAID:CA228410 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline FamilyInfo inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
22. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  32 K
  
  Case: Patient 32, Family K (Table 1.), F/17, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 18 (F/53, Afro-Carribean), Patient 29 (F/33, Afro-Caribbean), Patient 33 (F/49, Afro-Caribbean) also from Family K. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =4, FVIII:C (IU/dL) = 79, VWF:Ag (IU/dL) = 49, VWF:Act (IU/dL) = 37
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood type O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.2365A > G, p.(Thr789Ala)
  
  HGVS: NM_000552.5:c.2365A>G (p.Thr789Ala)
  
  ClinVarID: 256659
  
  CAID: CA6403090
  
  gnomAD: MAF of 0.5793 (43409/74928 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6044368-T-C?dataset=gnomad_r4
  
  Variant: c.2385T > C, p.(Tyr795 =)
  
  HGVS: NM_000552.5:c.2385T>C (p.Tyr795=)
  
  ClinVarID: 256660
  
  CAID: CA6403087
  
  gnomAD: MAF of 0.5788 (43385/74952 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6044348-A-G?dataset=gnomad_r4
  
  Variant: c.2880G > A, p.(Arg960 =)
  
  HGVS: NM_000552.5:c.2880G>A (p.Arg960=)
  
  ClinVarID: 195657
  
  CAID: CA201877
  
  gnomAD: MAF of 0.3169 (23737/74896 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6029429-C-T?dataset=gnomad_r4
  
  Variant: c.3505T > A, p.(Cys1169Ser)
  
  HGVS: NM_000552.5:c.3505T>A (p.Cys1169Ser)
  
  ClinVarID:
  
  CAID: CA383511219
  
  gnomAD:
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo Zygosity:CompoundHeterozygous ClinVarID:256659 CAID:CA6403090 ClinVarID:256660 CAID:CA6403087 ClinVarID:195657 CAID:CA201877 CAID:CA383511219 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
23. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  39 S
  
  Case: Patient 39, Family S (Table 1.), F/76, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIA)
  
  FamilyInfo: Patient 40 (F/38, Afro-Caribbean), Patient 41 (M/63, Afro-Caribbean) and Patient 52 (F/48, Afro Caribbean) also from Family S. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 3, FVIII:C (IU/dL) = 74, VWF:Ag (IU/dL) = 35, VWF:Act (IU/dL) = 12
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: deletion of exons 9-10
  
  HGVS: NM_000552.5:c.1030_1317del (p.Gly344_Arg439del)
  
  ClinVarID:
  
  CAID: CA3260663889
  
  gnomAD:
  
  Variant: c.4138A > G, p.(Ile1380Val)
  
  HGVS: NM_000552.5:c.4138A>G (p.Ile1380Val)
  
  ClinVarID: 310063
  
  CAID: CA6402595
  
  gnomAD: MAF of 0.1184 (8878/74958 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019280-T-C?dataset=gnomad_r4
  
  Variant: c.4304A > G, p.(Asn1435Ser)
  
  HGVS: NM_000552.5:c.4304A>G (p.Asn1435Ser)
  
  ClinVarID: 310062
  
  CAID: CA6402552
  
  gnomAD: MAF of 0.1124 (8427/74964 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019114-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.4628C > G p.(Ser1543Cys)
  
  HGVS: NM_000552.5:c.4628C>G (p.Ser1543Cys)
  
  ClinVarID: 4533008
  
  CAID: CA383500651
  
  gnomAD:
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo CAID:CA3260663889 ClinVarID:310063 CAID:CA6402595 ClinVarID:310062 CAID:CA6402552 ClinVarID:256679 CAID:CA6402534 ClinVarID:4533008 CAID:CA383500651 AlleleOrigin:Germline Zygosity:CompoundHeterozygous inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
24. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  9 F
  
  Case: Patient 9, Family F (Table 1.), F/76, Afro-Caribbean
  
  DiseaseAssertion: VWD2A (IIE)
  
  FamilyInfo: Patient 8 (M/86, Afro-Caribbean) and Patient 28 (F/55, Afro-Caribbean) also from Family F. (Table 1.)
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT =11, FVIII:C (IU/dL) = 40, VWF:Ag (IU/dL) = 30, VWF:Act (IU/dL) = 28
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group B-
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.1530G > A, p.(Val510 =) p.
  
  HGVS: NM_000552.5:c.1530G>A (p.Val510=)
  
  ClinVarID:
  
  CAID: CA6403368
  
  gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
  
  Variant: c.1892C > T, p.(Ala631Val)
  
  HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
  
  ClinVarID: 422844
  
  CAID: CA6403245
  
  gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
  
  Variant: c.2220G > A, p.(Met740Ile)
  
  HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
  
  ClinVarID: 100206
  
  CAID: CA201316
  
  gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
  
  Variant: c.2451T > A, p.(His817Gln)
  
  HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
  
  ClinVarID: 100224
  
  CAID: CA228345
  
  gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
  
  Variant: c.3426T > C, p.(Cys1142 =)
  
  HGVS: NM_000552.5:c.3426T>C (p.Cys1142=)
  
  ClinVarID: 256668
  
  CAID: CA6402757
  
  gnomAD: MAF of 0.2077 (7935/38206 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022852-A-G?dataset=gnomad_r4
  
  Variant: c.3445T > C, p.(Cys1149Arg)
  
  HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
  
  ClinVarID: 309
  
  CAID: CA228410
  
  gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?dataset=gnomad_r4
  
  Variant: c.3485C > T, p.(Pro1162Leu)
  
  HGVS: NM_000552.5(VWF):c.3485C>T (p.Pro1162Leu)
  
  ClinVarID: 256669
  
  CAID: CA6402756
  
  gnomAD: MAF of 0.2076 (7087/34136 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022793-G-A?dataset=gnomad_r4
  
  Variant: c.3486A > G, p.(Pro1162 =)
  
  HGVS: NM_000552.5:c.3486A>G (p.Pro1162=)
  
  ClinVarID: 256670
  
  CAID: CA6402755
  
  gnomAD: MAF of 0.2083 (7074/33968 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6022792-T-C?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Variant: c.6554G > A, p.(Arg2185Gln)
  
  HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
  
  ClinVarID: 100443
  
  CAID: CA228748
  
  gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2A FamilyInfo Zygosity:CompoundHeterozygous Zygosity:Homozygous CAID:CA6403368 ClinVarID:422844 CAID:CA6403245 ClinVarID:100206 CAID:CA201316 ClinVarID:100224 CAID:CA228345 ClinVarID:256668 CAID:CA6402757 ClinVarID:309 CAID:CA228410 ClinVarID:256669 CAID:CA6402756 ClinVarID:256670 CAID:CA6402755 ClinVarID:256679 CAID:CA6402534 ClinVarID:100443 CAID:CA228748 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
25. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  45 V
  
  Case: Patient 45, Family V (Table 1.), M/51, Afro-Caribbean
  
  DiseaseAssertion: VWD2M
  
  FamilyInfo: NA
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: BAT = 5, FVIII:C (IU/dL) = 45, VWF:Ag (IU/dL) = 96, VWF:Act (IU/dL) = 59
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText: Blood group O+
  
  CasePreviousTesting:
  
  GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant: c.4196G > A, p.(Arg1399His)
  
  HGVS: NM_000552.5:c.4196G>A (p.Arg1399His)
  
  ClinVarID: 293
  
  CAID: CA114133
  
  gnomAD: MAF of 0.01540 (456/29604 alleles) in Ashkenazi Jewish population https://gnomad.broadinstitute.org/variant/chr12-6019222-C-T?dataset=gnomad_r4
  
  Variant: c.4414G > C p.(Asp1472His)
  
  HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)
  
  ClinVarID: 256679
  
  CAID: CA6402534
  
  gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2M Zygosity:CompoundHeterozygous ClinVarID:293 CAID:CA114133 ClinVarID:256679 CAID:CA6402534 AlleleOrigin:Germline inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
Visit annotations in context

Tags

ClinVarID:293

CaseInfo

CAID:CA2695216024

ClinVarID:256660

ClinVarID:256679

CAID:CA6402595

CAID:CA114133

ClinVarID:310062

ClinVarID:100450

ClinVarID:256670

CAID:CA201877

CAID:CA228760

inferred_gene_source:CAID

Gene:VWF

CAID:CA6402950

ClinGen VWF

Zygosity:CompoundHeterozygous

CAID:CA228345

ClinVarID:256664

ClinVarID:256659

CAID:CA3260663889

ClinVarID:256668

CAID:CA6402959

CAID:CA201316

ClinVarID:256669

CAID:CA6402755

DiseaseEntity:VWD1

ClinVarID:802812

FamilyInfo

CAID:CA6403090

CAID:CA6403368

DiseaseEntity:VWD2M

CAID:CA228410

ClinVarID:1336650

ClinVarID:100206

ClinVarID:195657

CAID:CA6402534

CAID:CA383500651

Individual

ClinVarID:100443

ClinVarID:422844

Zygosity:Homozygous

ClinVarID:310063

CAID:CA228748

CAID:CA383511219

ClinVarID:2500546

ClinVarID:100224

ClinVarID:4533008

AlleleOrigin:Germline

ClinVarID:309

CAID:CA6402788

CAID:CA6402756

DiseaseEntity:VWD2A

CAID:CA6403087

inferred_gene_hgnc:12726

CAID:CA6403245

CAID:CA6402852

CAID:CA6402552

CAID:CA6402757

Annotators

ClingenBaseline

URL

pmc.ncbi.nlm.nih.gov/articles/PMC12175117/
www.sciencedirect.com www.sciencedirect.com

Common large partial VWF gene deletion does not cause alloantibody formation in the Hungarian type 3 von Willebrand disease population

5
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 23< 1110−−23FdelEx1‐3/c.2435delCdelEx1‐3/p.P812RfsX311–3/1818/19N/PD
 
 Case: Patient 2, F, Hungarian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: compatible with recessive inheritance
 
 ParentalGenotype(s): n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeRext: Bleeding score: 23, VWF:Ag (IU dL−1): < 1, VWF:CB (IU dL−1): 1, FVIII:C (IU dL−1): 10, VWF:RCo below detection limit (<10 IU dL−1), not detectable VWF on multimer gels, bleeding episode severity increased after the menarche
 
 CaseNOTHPOs: n/a
 
 CaseNOTHPOFreeText: no inhibitor detected, did not become refractory to factor replacement therapy
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 delEx1‐3 (delEx1‐3), Exon 1–3
 
 c.2435delC (p.Pro812ArgfsX31), Exon 18
 
 Intron 40 VNTR: 18/19
 
 Note: multimer electrophoresis, Recombinant VWF antigen concentrations and Collagen binding activity (VWF:CB) measured by ELISA, direct sequencing of the 51 exons and the exon‐intron boundaries, Breakpoint analysis and breakpoint‐specific PCR
 
 Mutation:Large Mutation:Frameshift DiseaseEntity:VWD3 Zygosity:CompoundHeterozygous CAID:CA114153 Mutation:delEx1‐3 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
2. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 183< 1< 13−−20Mc.1992insC/c.5557C>Tp.C665LfsX13/p.R1853X16/3215/16N/PD
 
 Case: Patient 18, M, Hungarian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: compatible with recessive inheritance
 
 ParentalGenotype(s): n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeRext: Bleeding score: 20, VWF:Ag (IU dL−1): < 1, VWF:CB (IU dL−1): < 1, FVIII:C (IU dL−1): 3, VWF:RCo below detection limit (<10 IU dL−1), not detectable VWF on multimer gels
 
 CaseNOTHPOs: n/a
 
 CaseNOTHPOFreeText: no inhibitor detected, did not become refractory to factor replacement therapy
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 c.1992insC (p.Cys665LeufsX13), Exon 16
 
 c.5557C>T (p.Arg1853X), Exon 32
 
 Intron 40 VNTR 15/16
 
 Note: multimer electrophoresis, Recombinant VWF antigen concentrations and Collagen binding activity (VWF:CB) measured by ELISA, direct sequencing of the 51 exons and the exon‐intron boundaries, Breakpoint analysis and breakpoint‐specific PCR
 
 DiseaseEntity:VWD3 Mutation:Frameshift Mutation:Nonsense Zygosity:CompoundHeterozygous CAID:CA2617232074 CAID:CA114143 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
3. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 203< 1< 16−14Mc.103T>C/c.4975C>Tp.C35R/p.R1659X3/2814/16N/PD
 
 Case: Patient 20, M, Hungarian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: compatible with recessive inheritance
 
 ParentalGenotype(s): n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeRext: Bleeding score: 14, VWF:Ag (IU dL−1): < 1, VWF:CB (IU dL−1): < 1, FVIII:C (IU dL−1): 6, VWF:RCo below detection limit (<10 IU dL−1), not detectable VWF on multimer gels
 
 CaseNOTHPOs: n/a
 
 CaseNOTHPOFreeText: did not become refractory to factor replacement therapy
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 c.103T>C (p.Cys35Arg), Exon 3
 
 c.4975C>T (p.Arg1659X), Exon 28
 
 Intron 40 VNTR 14/16
 
 Note: multimer electrophoresis, Recombinant VWF antigen concentrations and Collagen binding activity (VWF:CB) measured by ELISA, direct sequencing of the 51 exons and the exon‐intron boundaries, Breakpoint analysis and breakpoint‐specific PCR
 
 DiseaseEntity:VWD3 Mutation:Missense CAID:CA383508776 Mutation:Nonsense Zygosity:CompoundHeterozygous CAID:CA114141 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
4. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 103< 1< 13−−18Mc.2269_2270delCT/c.2435delCp.L757VfsX22/p.P812RfsX3117/1817/18PD/PD
 
 Case: Patient 10, M, Hungarian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: compatible with recessive inheritance
 
 ParentalGenotype(s): n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeRext: Bleeding score: 18, VWF:Ag (IU dL−1): < 1, VWF:CB (IU dL−1): < 1, FVIII:C (IU dL−1): 3, VWF:RCo below detection limit (<10 IU dL−1), not detectable VWF on multimer gels
 
 CaseNOTHPOs: n/a
 
 CaseNOTHPOFreeText: no inhibitor detected, did not become refractory to factor replacement therapy
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 c.2269_2270delCT (p.L757VfsX22), Exon 17
 
 c.2435delC (p.P812RfsX31), Exon 18
 
 Intron 40 VNTR: 17/18
 
 Note: multimer electrophoresis, Recombinant VWF antigen concentrations and Collagen binding activity (VWF:CB) measured by ELISA, direct sequencing of the 51 exons and the exon‐intron boundaries, Breakpoint analysis and breakpoint‐specific PCR
 
 DiseaseEntity: VWD3 Mutation:Frameshift Zygosity:CompoundHeterozygous CAID:CA228313 CAID:CA114153 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
5. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 173< 1< 14−−18Fc.7333delG/c.7703C>Ap.E2445RfsX16/p.S2568X43/4517/18N/N
 
 Case: Patient 17, F, Hungarian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: compatible with recessive inheritance
 
 ParentalGenotype(s): n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeRext: Bleeding score: 18, VWF:Ag (IU dL−1): < 1, VWF:CB (IU dL−1): < 1, FVIII:C (IU dL−1): 4, VWF:RCo below detection limit (<10 IU dL−1), not detectable VWF on multimer gels, bleeding episode severity increased after the menarche
 
 CaseNOTHPOs: n/a
 
 CaseNOTHPOFreeText: no inhibitor detecteddid not become refractory to factor replacement therapy
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 c.7333delG (p.Glu2445ArgfsX16), Exon 43
 
 c.7703C>A (p.Ser2568X), Exon 45
 
 Intron 40 VNTR 17/18
 
 Note: multimer electrophoresis, Recombinant VWF antigen concentrations and Collagen binding activity (VWF:CB) measured by ELISA, direct sequencing of the 51 exons and the exon‐intron boundaries, Breakpoint analysis and breakpoint‐specific PCR
 
 DiseaseEntity:VWD3 Mutation:Frameshift Zygosity:CompoundHeterozygous Mutation:Nonsense CAID:CA2617226909 CAID:CA383489253 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
Visit annotations in context

Tags

CAID:CA2617232074

DiseaseEntity:VWD3

CAID:CA228313

CAID:CA2617226909

inferred_gene_source:CAID

Mutation:Nonsense

ClinGen VWF

Zygosity:CompoundHeterozygous

CAID:CA383489253

Mutation:Large

Mutation:Missense

CAID:CA114141

CAID:CA383508776

CAID:CA114143

inferred_gene_hgnc:12726

Mutation:delEx1‐3

CAID:CA114153

Mutation:Frameshift

DiseaseEntity: VWD3

Annotators

ClingenBaseline

URL

sciencedirect.com/science/article/pii/S1538783622069197
www.sciencedirect.com www.sciencedirect.com

Molecular defects in type 3 von Willebrand disease: updated results from 40 multiethnic patients

8
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 6ItalyF/15<1—NoSevere2269delCT/7729+7C→TFS/FS17/45HeterozygousEsp3I (+)/NlaIII (−)
 
 Case: 6 , F, 15, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 2269delCT (FS), Exon 17
 
 7729+7C→T (intronic), Exon 45
 
 Compound Heterozygous
 
 Note: Article assumes that 7729+7C→T would be a frameshift mutation. No potential splice site mutation was confirmed at the mRNA level; “Splice Site Prediction program” found all mutations likely to disrupt normal splicing. No possible splice site mutation could be identified on 100 chromosomes from a group of 50 normal subjects with same genetic background as patients, excluding the possibility that these mutations represent common polymorphisms.
 
 DiseaseEntity:VWD3 Mutation:Intronic Mutation:Frameshift Zygosity:CompoundHeterozygous CAID:CA228815 CAID:CA228313 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
2. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 7*ItalyF/36<1—NoSevere2435delC/5170+10C→T 253T→CFS/FS-S85P18/29-4HeterozygousBglI (−)/N.A.
 
 Case: 7 , F, 36, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype:
 
 2435delC on the maternal allele
 
 5170+10C→T on the paternal allele
 
 253T→C on the paternal allele
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 2435delC (FS), Exon 18
 
 5170+10C→T (Intronic), Exon 29
 
 253T→C (Ser85Pro), Exon 4
 
 Compound Heterozygous
 
 Note: Article assumes that 5170+10C→T would be a frameshift mutation. No potential splice site mutation was confirmed at the mRNA level; “Splice Site Prediction program” found all mutations likely to disrupt normal splicing. No possible splice site mutation could be identified on 100 chromosomes from a group of 50 normal subjects with same genetic background as patients, excluding the possibility that these mutations represent common polymorphisms.
 
 DiseaseEntity:VWD3 Mutation:Frameshift PreviouslyPublished Mutation:Missense Mutation:Intronic CAID:CA228348 Zygosity:CompoundHeterozygous CAID:CA114153 CAID:CA228702 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
3. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 39IndiaM/33<1—NoMild4092delAC/7130insCFS/FS28/42HeterozygousN.A./N.A.
 
 Case: 39, M, 33, Indian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: No
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 4092delAC (FS), Exon 28
 
 7130insC (FS), Exon 42
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 Mutation:Frameshift Zygosity:CompoundHeterozygous CAID:CA228774 CAID:CA228532 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
4. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 3*ItalyF/21<1—NoSevere666G→A/823T→AW222X/C275S7/7HeterozygousN.A./BsrI (+)
 
 Case: 3, F, 21, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 666G→A (Trp222X), Exon 7
 
 823T→A (Cys275Ser), Exon 7
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 Mutation:Missense PreviouslyPublished Mutation:Nonsense CAID:CA228834 Zygosity:CompoundHeterozygous CAID:CA228753 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
5. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 2ItalyF/58<1—NoSevere421G→T/2016del4D141Y/FS5/16HeterozygousBstYI (+)/N.A.
 
 Case: 2, F, 58, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 421G→T (Asp141Tyr), Exon 5
 
 2016del4 (FS), Exon 16
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 Mutation:Frameshift Mutation:Missense CAID:CA228559 Zygosity:CompoundHeterozygous CAID:CA228305 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
6. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 8*ItalyF/7<1—NoMild4013C→G/6385G→TS1338X/E2129X28/37HeterozygousN.A./MnlI (−)
 
 Case: 8, F, 7, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 4013C→G (Ser1338X), Exon 28
 
 6385G→T (Glu2129X), Exon 37
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 PreviouslyPublished Mutation:Nonsense Zygosity:CompoundHeterozygous CAID:CA228512 CAID:CA228738 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
7. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 4ItalyM/55<1—NoSevere1093C→T/1830C→AR365X/Y610X9/15HeterozygousTaqI (−)/DdeI (+)
 
 Case: 4 , M, 55, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 1093C→T (Arg365X), Exon 9
 
 1830C→A (Tyr610X), Exon 15
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 Mutation:Nonsense Zygosity:CompoundHeterozygous CAID:CA228257 CAID:CA228289 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
8. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 37IndiaF/29<1—NoMild1896G→A/3212G→TW642X/C1071F15/24HeterozygousMaeIII (+)/N.A.
 
 Case: 37, F, 29, Indian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: No
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 1896G→A (Trp642X), Exon 15
 
 3212G→T (Cys1071Phe), Exon 24
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 Mutation:Nonsense Mutation:Missense CAID:PA228301 CAID:CA228382 Zygosity:CompoundHeterozygous inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
Visit annotations in context

Tags

CAID:CA228257

DiseaseEntity:VWD3

CAID:CA228313

CAID:CA228532

CAID:CA228512

CAID:CA228305

CAID:CA228753

inferred_gene_source:CAID

CAID:CA228289

Mutation:Intronic

CAID:CA228834

Mutation:Nonsense

ClinGen VWF

Zygosity:CompoundHeterozygous

CAID:CA228559

CAID:CA228702

Mutation:Missense

CAID:CA228815

CAID:CA228738

CAID:CA228382

inferred_gene_hgnc:12726

CAID:CA114153

CAID:CA228348

CAID:CA228774

Mutation:Frameshift

CAID:PA228301

PreviouslyPublished

Annotators

ClingenBaseline

URL

sciencedirect.com/science/article/pii/S1079979603000330
www.sciencedirect.com www.sciencedirect.com

The genetics of Canadian type 3 von Willebrand disease: further evidence for co-dominant inheritance of mutant alleles

7
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  T046F/16210.010.040.02c.385C>A, c.813C>Ap.Leu129Met, p.Tyr271*5/7Compound heterozygous
  
  Case: T046, F, 16
  
  DiseaseAssertion: VWD type 3
  
  FamilyInfo: n/a
  
  CasePresentingHPOs: n/a
  
  CaseHPOFreeText: Bleeding Score: 21 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.01, VWF:RCo (IU/ml): 0.04, FVIII:C (IU/ml): 0.02
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: n/a
  
  CasePreviousTesting: n/a
  
  Gene: VWF
  
  Variant:
  
  c.385C>A (p.Leu129Met), Exon 5
  
  c.813C>A (p.Tyr271*), Exon 7
  
  Compound heterozygous
  
  Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
  
  DiseaseEntity:VWD3 Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAID:CA228468 CAID:CA383508534 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
2. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  T154M/16240.010.030.01c.1656_1657insT, c.8418_8419insTCCCp.Trp552 fs, p.Ser2807 fs14/52Compound heterozygous
  
  Case: T154, M, 16
  
  DiseaseAssertion: VWD type 3
  
  FamilyInfo: n/a
  
  CasePresentingHPOs: n/a
  
  CaseHPOFreeText: Bleeding Score: 24 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.01, VWF:RCo (IU/ml): 0.03, FVIII:C (IU/ml): 0.01
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: n/a
  
  CasePreviousTesting: n/a
  
  Gene: VWF
  
  Variant:
  
  c.1656_1657insT (p.Trp552 fs), Exon 14
  
  c.8418_8419insTCCC (p.Ser2807 fs), Exon 52
  
  Compound heterozygous
  
  Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
  
  DiseaseEntity:VWD3 Mutation:Frameshift Zygosity:CompoundHeterozygous CAID:CA228279 CAID:CA690454659 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
3. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  T018F/18120.040.000.03c.7399C>T, c.8418_8419insTCCCp.Gln2467*, p.Ser2807 fs43/52Compound heterozygous
  
  Case: T018, F, 12
  
  DiseaseAssertion: VWD type 3
  
  FamilyInfo: n/a
  
  CasePresentingHPOs: HP:0000421
  
  CaseHPOFreeText: Bleeding Score: 12 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.04, VWF:RCo (IU/ml): 0.00, FVIII:C (IU/ml): 0.03, inhibitor positive
  
  CaseNotHPOs: has not developed any anaphylactic reactions and/or become refractory to replacement therapy
  
  CaseNotHPOFreeText: n/a
  
  CasePreviousTesting: n/a
  
  Gene: VWF
  
  Variant:
  
  c.7399C>T (p.Gln2467*), Exon 43
  
  c.8418_8419insTCCC (p.Ser2807 fs), Exon 52
  
  Compound heterozygous
  
  Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
  
  DiseaseEntity:VWD3 Mutation:Nonsense Mutation:Frameshift Zygosity:CompoundHeterozygous CAID:CA690454659 CAID:CA383490368 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
4. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  T030M/6670.030.010.09c.-2328T>G, c.2220G>A, c.3379 + 7A>C, c.3539-33G>A, c.3539-49C>T, c.4414dupC, c.5620 + 33-40delA, c.6554G>A, c.6902-5T>A, c.8418_8419insTCCCp.Met740Ile, p.His1472 fs, p.Arg2185Gln, p.Ser2807 fs28/52Compound heterozygous
  
  Case: T030, M, 66
  
  DiseaseAssertion: VWD type 3
  
  FamilyInfo: n/a
  
  CasePresentingHPOs: n/a
  
  CaseHPOFreeText: Bleeding Score: 7 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.03, VWF:RCo (IU/ml): 0.01, FVIII:C (IU/ml): 0.09
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: n/a
  
  CasePreviousTesting: n/a
  
  Gene: VWF
  
  Variant:
  
  c.-2328T>G
  
  c.2220G>A (p.Met740Ile)
  
  c.3379 + 7A>C
  
  c.3539-33G>A
  
  c.3539-49C>T
  
  c.4414dupC (p.His1472 fs)
  
  c.5620 + 33-40delA
  
  c.6554G>A (p.Arg2185Gln)
  
  c.6902-5T>A
  
  c.8418_8419insTCCC (p.Ser2807 fs)
  
  Exon 28/52
  
  Compound heterozygous
  
  Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
  
  DiseaseEntity:VWD3 Mutation:Missense Mutation:Frameshift Zygosity:CompoundHeterozygous Mutation:Intronic CAID:CA201316 CAID:CA228748 CAID:CA6402765 Mutation:c.-2328T>G CAID:CA6402748 CAID:CA6402753 CAID:CA228594 Mutation:c.5620+33-40delA CAID:CA6401849 CAID:CA690454659 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
5. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  T086M/130.010.020.01c.1A>G, c.2377C>Tp.Met1Val, p.Gln793*2/18Compound heterozygous
  
  Case: T086, M, 1
  
  DiseaseAssertion: VWD type 3
  
  FamilyInfo: n/a
  
  CasePresentingHPOs: n/a
  
  CaseHPOFreeText: Bleeding Score: 3 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.01, VWF:RCo (IU/ml): 0.02, FVIII:C (IU/ml): 0.01
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: n/a
  
  CasePreviousTesting: n/a
  
  Gene: VWF
  
  Variant:
  
  c.1A>G (p.Met1Val), Exon 2
  
  c.2377C>T (p.Gln793*), Exon 18
  
  Compound Heterozygous
  
  Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
  
  DiseaseEntity:VWD3 Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAID:CA383522113 CAID:CA383510938 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
6. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  T050F/21240.010.000.01c.876delC, c.1255C>Tp.Ser293 fs, p.Gln419*8/11Compound heterozygous
  
  Case: T050, F, 21
  
  DiseaseAssertion: VWD type 3
  
  FamilyInfo: n/a
  
  CasePresentingHPOs: n/a
  
  CaseHPOFreeText: Bleeding Score: 24 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.01, VWF:RCo (IU/ml): 0.00, FVIII:C (IU/ml): 0.01
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: n/a
  
  CasePreviousTesting: n/a
  
  Gene: VWF
  
  Variant:
  
  c.876delC (p.Ser293 fs), Exon 8
  
  c.1255C>T (p.Gln419*), Exon 11
  
  Compound heterozygous
  
  Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
  
  DiseaseEntity:VWD3 Mutation:Nonsense Mutation:Frameshift Zygosity:CompoundHeterozygous CAID:CA2575054279 CAID:CA232314778 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
7. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  T090M/280.010.040.01c.1117C>T, gene conversion (c.3931C>T, c.4027A>G, c.4079T>C, c.4105T>A)p.Arg373*, p.Gln1311*, p.Ile1343Val, p.Val1360Ala, p.Phe1369Ile10/28Compound heterozygous
  
  Case: T090, M, 2
  
  DiseaseAssertion: VWD type 3
  
  FamilyInfo: inherited heterozygous gene conversion from the father
  
  CasePresentingHPOs: n/a
  
  CaseHPOFreeText: Bleeding Score: 8 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.01, VWF:RCo (IU/ml): 0.04, FVIII:C (IU/ml): 0.01
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: n/a
  
  CasePreviousTesting: n/a
  
  Gene: VWF
  
  Variant:
  
  c.1117C>T (p.Arg373*)
  
  Gene Conversion (
  
  c.3931C>T (p.Gln1311*)
  
  c.4027A>G (p.Ile1343Val)
  
  c.4079T>C (p.Val1360Ala)
  
  c.4105T>A (p.Phe1369Ile)
  
  )
  
  Exon 10/28
  
  Compound heterozygous
  
  Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation
  
  DiseaseEntity:VWD3 Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAID:CA228520 CAID:CA228526 CAID:CA228533 CAID:CA228261 CAID:CA228496 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
Visit annotations in context

Tags

CAID:CA228526

CAID:CA6402753

CAID:CA201316

DiseaseEntity:VWD3

CAID:CA383510938

CAID:CA228520

CAID:CA383508534

CAID:CA2575054279

CAID:CA228261

CAID:CA383522113

CAID:CA6402748

CAID:CA6401849

CAID:CA228279

CAID:CA228533

CAID:CA6402765

Mutation:Missense

CAID:CA690454659

CAID:CA228468

CAID:CA228594

CAID:CA228748

inferred_gene_source:CAID

Mutation:Intronic

Mutation:Nonsense

ClinGen VWF

CAID:CA228496

Zygosity:CompoundHeterozygous

Mutation:c.5620+33-40delA

CAID:CA232314778

inferred_gene_hgnc:12726

Mutation:Frameshift

CAID:CA383490368

Mutation:c.-2328T>G

Annotators

ClingenBaseline

URL

sciencedirect.com/science/article/pii/S1538783622137827
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Protein S gene mutation c.946C > T (p.R316C) contributed to ischemic stroke in a man with von Willebrand disease type 3 caused by two novel VWF gene mutations, c.2328delT (p.A778Lfs* 23) and c.6521G > T (p.C2174F)

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  type 3‐VWD patient
  
  Case:44‐year‐old male patient
  
  DiseaseAssertion:type 3‐VWD patient
  
  FamilyInfo:positive family hsiory: The proband and his sister both had low FVIII:C (1 IU/dL) and VWF:Ag (3 IU/dL) levels, confirming the diagnosis of type 3 VWD. His father had nearly normal levels of FVIII:C (58 IU/dL) and VWF:Ag (57 IU/dL). His daughter had type 1 VWD with decreased FVIII:C (46 IU/dL) and VWF:Ag (19 IU/dL)., NGS identified a heterozygous VWF c.2328delT (p.A778Lfs*23) frame shift mutation only in the proband and his sister
  
  ParentalGenotype(s):VWF missense mutation, c.6521G > T (p.C2174F), was found heterozygous in father, but mother not tested
  
  CasePresentingHPOs:BAT score=16, Arterial thrombosis=ischemic stroke, FVIII:C*=1, VWF:Ag=3, Proein S:58, Protein C:100, antithrombin III=106, activated protein C resistance:2.9. CaseHPOFreeRext: Complete blood count showed normocytic anemia (hemoglobin 74 g/L), normal white cell (and differential), and platelet counts. He had prolonged activated partial thromboplastin time (APTT) (89.4 s (s) [reference range (RR), 28.0–44.0 s]) with greatly decreased FVIII:C (1 IU/dL) and VWF:Ag (3 IU/dL) (Table 1). Abdominal ultrasound scanning revealed fatty liver, normal gallbladder, spleen, pancreas, and kidneys. Four hundred ml of virus inactivated fresh frozen plasma (FFP) was transfused, and his VWF:Ag increased to 6 IU/dL. On Day 2 after admission, the patient abruptly experienced numbness and weakness in his right limb.
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText:
  
  CasePreviousTesting:n.a
  
  GenotypingMethod:NGS
  
  PreviouslyPublished: If applicable.
  
  Gene: VWF
  
  Variant:c.2328delT (p.A778Lfs*23) and c.6521G > T (p.C2174F)
  
  HGVS:n.a.
  
  ClinVarID:n.a.
  
  CAID:n.a.
  
  gnomAD: n.a.
  
  InheritancePattern:AutosomalRecessive Novel mutations DiseaseEntity:VWD3 AlleleOrigin:Germline Mutation:Missense Mutation:Frameshift Zygosity:CompoundHeterozygous UnregisteredVariant FamilyInfo ParentalTest:Paternity inferred_gene_hgnc:12726 inferred_gene_source:Gene_Name ClinGen VWF
Visit annotations in context

Tags

Mutation:Missense

DiseaseEntity:VWD3

InheritancePattern:AutosomalRecessive

inferred_gene_source:Gene_Name

Novel mutations

ParentalTest:Paternity

UnregisteredVariant

inferred_gene_hgnc:12726

FamilyInfo

ClinGen VWF

Mutation:Frameshift

AlleleOrigin:Germline

Zygosity:CompoundHeterozygous

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC9399824/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Outcome of Patients with Classical Infantile Pompe Disease Receiving Enzyme Replacement Therapy in Germany

3
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 16
 
 Case#: P 16, Female, 3.4 months old when started ERT (Died at 27.0 months), German
 
 DiseaseAssertion: Pompe disease
 
 FamilyInfo: N/A
 
 CasePresentingHPOs: P:0001639 , HP:0001252 , HP:0003701, HP:0002090
 
 (Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Pneumonia)
 
 CaseHPOFreeText: Pneumonia, deterioration and AR III were complications during ERT)
 
 Ventilation and tube feeding were necessary
 
 Best motor status was sitting
 
 CaseNotHPOs: N/A
 
 CaseNotHPOFreeText: N/A
 
 CasePreviousTesting: CRIM status was positive
 
 Antibody titer 1:5,600
 
 Variant: NM_000152.5(GAA):c.1548G>A (p.Trp516Ter)
 
 ClinVar: 189025
 
 CAID: CA274281
 
 gnomAD: MAF=0.00001552 in European non-Finnish
 
 Variant: c.IVS14 + 20A>G (old nomenclature)
 
 ClinVar: N/A
 
 CAID: N/A
 
 gnomAD: N/A
 
 ParentalGenotype: The maternal allele carried the c.IVS14 + 20A>G variant
 
 The paternal allele carried the c.1548G>A Variant
 
 PreviouslyPublished: N/A
 
 CaseInfo Individual DiseaseEntity:PompeDisease Zygosity:CompoundHeterozygous ParentalTest:FullPhase PreviousTesting:NoGAAmeasurement ClinVarID:189025 CAid:CA274281 inferred_gene_hgnc:4065 inferred_gene_source:CAID GAA variant
2. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 2
 
 Case#: P 2, Female, 4.7 months old when started ERT (113.7 months old at publication date), ethnicity unknown
 
 DiseaseAssertion: Pompe disease
 
 FamilyInfo: Table 1 includes parental genotype
 
 CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0002090
 
 (Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Pneumonia)
 
 CaseHPOFreeText: Aspiration pneumonia was a complication during ERT.
 
 Patient requires tube feeding.
 
 Patient's best and current motor status is being able to sit.
 
 CaseNotHPOs: N/A
 
 CaseNotHPOFreeText: Patient has not required ventilation
 
 CasePreviousTesting: CRIM status is positive in patient
 
 Antibody titer is 1:1.200
 
 Variant 1: NM_000152.5(GAA):c.1799G>A (p.Arg600His)
 
 ClinVar: 370130
 
 CAID: CA8815482
 
 gnomAD: Highest population MAF= 0.00003267 in South Asians
 
 Variant 2: c.1859G>A
 
 ClinVar: N/A
 
 CAID: N/A
 
 gnomAD: N/A
 
 ParentalGenotype: Mother is the carrier of the c.1799G>A (p.Arg600His) Variant
 
 Father is the carrier of the c.1859G>A variant
 
 PreviouslyPublished: N/A
 
 CaseInfo Individual Zygosity:CompoundHeterozygous DiseaseEntity:PompeDisease ParentalTest:FullPhase PreviousTesting:NoGAAmeasurement UnregisteredVariant ClinVarID:370130 CAid:CA8815482 inferred_gene_hgnc:4065 inferred_gene_source:CAID GAA variant
3. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 22
 
 Case#: P 22, Female, 0.2 months old when started ERT (47.0 months old when last reported), German
 
 DiseaseAssertion: Pompe disease
 
 FamilyInfo: N/A
 
 CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0001371
 
 (Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Flexion contracture )
 
 CaseHPOFreeText: Flexion contractures were a complication during ERT
 
 CaseNotHPOs: N/A
 
 CaseNotHPOFreeText: No tube feeding nor ventilation needed
 
 CasePreviousTesting: CRIM status is unknown
 
 Antibody titer is 1:1.800
 
 Variant 1: NM_000152.3:c.2004C>A
 
 ClinVar: N/A
 
 CAID: CA401370054
 
 gnomAD: N/A
 
 Variant: c.541545delTTAC
 
 ClinVar: N/A
 
 CAID: N/A
 
 gnomAD: N/A
 
 ParentalGenotype: Maternal allele carried the c.2004 C>A Variant
 
 The paternal allele carried the c.541545delTTAC
 
 PreviouslyPublished: N/A
 
 CaseInfo Individual DiseaseEntity:PompeDisease ParentalTest:FullPhase InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous UnregisteredVariant CAid:CA401370054 inferred_gene_hgnc:4065 inferred_gene_source:CAID GAA variant
Visit annotations in context

Tags

ClinVarID:189025

inferred_gene_hgnc:4065

inferred_gene_source:CAID

UnregisteredVariant

Zygosity:CompoundHeterozygous

CAid:CA274281

CaseInfo

CAid:CA401370054

DiseaseEntity:PompeDisease

InheritancePattern:AutosomalRecessive

Individual

ClinVarID:370130

GAA variant

ParentalTest:FullPhase

PreviousTesting:NoGAAmeasurement

CAid:CA8815482

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC4375117/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Clinical course, mutations and its functional characteristics of infantile-onset Pompe disease in Thailand

1
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 3
 
 Case#: Patient 3, Gender N/A, 5-6 months old when diagnosed.13 months when died, Southeast Asian
 
 DiseaseAssertion: Pompe disease
 
 FamilyInfo:
 
 CasePresentingHPOs: HP:0002094 HP:0001639. HP:0005165 (Hypertrophic Cardiomyopathy, Dyspnea, Shortened PR interval)
 
 CaseHPOFreeText: Generalized Muscle weakness
 
 CaseNotHPOs: N/A
 
 CaseNotHPOFreeText: N/A
 
 CasePreviousTesting: GAA enzyme activity in leukocytes was 0% of the normal control value.
 
 PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions
 
 Variant1: NM_000152.5(GAA):c.1099T>C (p.Trp367Arg)
 
 ClinVar: 555820
 
 CAID: CA401364951
 
 gnomAD: N/A
 
 Variant2: NM_000152.5(GAA):c.1942G>A (p.Gly648Ser)
 
 ClinVar: 188902
 
 CAID: CA274102
 
 gnomAD: Highest population MAF = 0.0003365 (South Asian)
 
 ParentalGenotype: Father was carrier for Variant1 NM_000152.5(GAA):c.1099T>C (p.Trp367Arg)
 
 Mother was carrier of Variant 2 NM_000152.5(GAA):c.1942G>A (p.Gly648Ser)
 
 PreviouslyPublished: N/A
 
 CaseInfo Individual DiseaseEntity:PompeDisease Zygosity:CompoundHeterozygous ClinVarID:555820 ClinVarID:188902 CAid:CA274102 CAid:CA401364951 inferred_gene_hgnc:4065 inferred_gene_source:CAID GAA variant
Visit annotations in context

Tags

DiseaseEntity:PompeDisease

ClinVarID:188902

inferred_gene_hgnc:4065

CAid:CA401364951

Individual

ClinVarID:555820

inferred_gene_source:CAID

GAA variant

Zygosity:CompoundHeterozygous

CaseInfo

CAid:CA274102

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC6737665/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Pearls & Oy-sters: Clues to the diagnosis of adult-onset acid maltase deficiency

2
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  PATIENT 2
  
  Case#: Patient 2, Male, 71 year old, ethnicity unknown
  
  DiseaseAssertion: Pompe disease
  
  diagnosed at age 52 with SMA type III following an EMG reporting neurogenic changes and a muscle biopsy from a hamstring muscle that demonstrated denervation atrophy
  
  FamilyInfo: N/A
  
  CasePresentingHPOs: HP:0003701, HP:0003445
  
  (Proximal muscle weakness, EMG:neuropathic changes
  
  CaseHPOFreeText: Normal strength in the upper extremities with moderate weakness of hip flexion at 3/5, hip abduction 3–4/5, hip adduction 3–4/5, and hamstrings 4/5.
  
  EMG showed myotonic discharges in the anterior tibialis, medial gastrocnemius, iliopsoas, tensor fasciae latae, and biceps brachii muscles.
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: N/A
  
  Staining for PAS and acid phosphatase was normal.
  
  Serum CK was 208 U/L (normal range 70–185)
  
  CasePreviousTesting: GAA activity was 1.3pmol/punch/h (normal 10–49 pmol/punch/h) and he was found to have 2 heterozygous mutations
  
  Variant 1: NM_000152.5(GAA):c.-32-13T>G
  
  ClinVar: 4027
  
  CAID: CA116606
  
  gnomAD: Highest population MAF= 0.005541 (Ashkenazi Jewish)
  
  Variant 2: NM_000152.5(GAA):c.1841C>A (p.Thr614Lys)
  
  ClinVar: 167113
  
  CAID: CA234050
  
  gnomAD: Highest population MAF= 0.00004784 (European nin-Finnish)
  
  ParentalGenotype:N/A
  
  PreviouslyPublished:N/A
  
  CaseInfo Individual DiseaseEntity:PompeDisease Zygosity:CompoundHeterozygous PreviousTesting:GAAmeasurement ParentalTest:None CAid:CA234050 ClinVarID:167113 ClinVarID:4027 CAid:CA116606 inferred_gene_hgnc:4065 inferred_gene_source:CAID GAA variant
2. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  PATIENT 1
  
  Case#: Patient 1, woman, 58 years old, ethnicity unknown
  
  DiseaseAssertion:Pompe disease
  
  Was also misdiagnosed with adult-onset spinal muscular atrophy (SMA)
  
  FamilyInfo: No family history of muscle disease
  
  CasePresentingHPOs: HP:0003701, HP:0100284
  
  (Proximal muscle weakness, EMG myotonic discharges)
  
  CaseHPOFreeText: Denervation atrophy from a muscle biopsy
  
  Weakness of hip flexion 2–3/5, hip abduction 2/5, and hip adduction 2/5
  
  Myotonic discharges were in the lumbar paraspinals, vastus medialis, and tensor fasciae latae muscles.
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: N/A
  
  CasePreviousTesting: GAA enzyme activity assay was 1 pmol/punch/h (normal range 10–49 pmol/punch/h)
  
  Her creatine kinase (CK) level at presentation had been elevated as high as 429 U/L (normal range 45–145)
  
  Found with two mutations in the GAA gene
  
  Variant: NM_000152.5(GAA):c.-32-13T>G
  
  ClinVar: 4027
  
  CAID: CA116606
  
  gnomAD: Highest population MAF= 0.005541 (Ashkenazi Jewish)
  
  Variant: NM_000152.5(GAA):c.525del (p.Glu176fs) Double check this variant
  
  ClinVar: 4033
  
  CAID: CA220406
  
  gnomAD: N/A
  
  ParentalGenotype:N/A
  
  Previously Published: N/A
  
  CaseInfo Individual DiseaseEntity:PompeDisease Zygosity:CompoundHeterozygous PreviousTesting:GAAmeasurement ParentalTest:None ClinVarID:4033 ClinVarID:4027 CAid:CA116606 CAid:CA220406 inferred_gene_hgnc:4065 inferred_gene_source:CAID GAA variant
Visit annotations in context

Tags

ClinVarID:4027

inferred_gene_hgnc:4065

CAid:CA234050

inferred_gene_source:CAID

ParentalTest:None

Zygosity:CompoundHeterozygous

CAid:CA220406

CaseInfo

DiseaseEntity:PompeDisease

PreviousTesting:GAAmeasurement

ClinVarID:4033

Individual

CAid:CA116606

ClinVarID:167113

GAA variant

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC3945654/
Local file Local file

CPLA_A_573600_P 547..551

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  In 1986, a preliminary report described a girl
  
  Case1: Female, 22 years old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: See Fig 1
  
  ParentalGenotype: The patient's parents revealed reduced concentrations of glycoprotein llb-Illa and were considered to be heterozygotes. See Fig 1
  
  CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0000978
  
  (Severe epistaxis, gingival bleeding, menorrhagia, spontaneous bruising)
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: N/A
  
  ProteinExpression: Platelets had much reduced alphaIIb3 when estimated by crossed immunoelectrophoresis
  
  PlateletAggregation: Platelet aggregation was absent with ADP, arachidonic acid, and collagen.
  
  CasePreviousTesting: Sequenced all exons and splice sites of ITGA2B and ITGB3
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)
  
  LegacyVariant: (p.Arg327His) and (p.Gly381Arg)
  
  ClinVar: 2896 and 381748
  
  CAiD: CA115839 and CA8603182
  
  gnomAD: MAF in the Latino population is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T
  
  PreviouslyPublished: PMID: 3762006 proband is mentioned in this article
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:2896 ClinVarID:381748 CAiD:CA115839 CAiD:CA8603182 PreviousTesting:Full FamilyInfo ParentalTesting:FullPhase ProteinExpression:Reported PlateletAggregation:Reported PreviouslyPublished inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

inferred_gene_hgnc:6138

CAiD:CA115839

PreviousTesting:Full

inferred_gene_source:CAID

FamilyInfo

ClinGen ITGA2B/ITGB3

CAiD:CA8603182

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

Individual

ClinVarID:2896

ClinVarID:381748

ProteinExpression:Reported

PlateletAggregation:Reported

PreviouslyPublished

Annotators

ClingenBaseline
reader.elsevier.com reader.elsevier.com

Hematologically Important Mutations: Glanzmann Thrombasthenia

8
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 RS
 
 Case37: Patient RS
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132
 
 (Epistaxis, gingival bleeding, menorrhagia)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: N/A
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.1260G>A and the other variant won't show up in CAR
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8623200
 
 gnomAD: MAF in the African population is 0.00004005 https://gnomad.broadinstitute.org/variant/17-45368454-G-A
 
 PreviouslyPublished: Reference 60
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous ProteinExpression:NotReported PlateletAggregation:NotReported PreviouslyPublished inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Family L
 
 Case15: Family L (patient found in the GT database as well) gender and age are not specified here
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0000225(Epistaxis, gingival bleeding)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: N/A
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1750C>T (p.Arg584Ter)
 
 LegacyVariant: N/A
 
 ClinVar: 2892
 
 CAiD: CA115834
 
 gnomAD: MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A
 
 PreviouslyPublished: Reference numbers 26,27 in this article
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous ClinVarID:2892 CAiD:CA115834 ProteinExpression:NotReported PlateletAggregation:NotReported PreviouslyPublished inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 GT3
 
 Case33: Patient GT3
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: Mucocutaneous bleeding
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: N/A
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.777+1G>A and the second variant I am not sure how to write out
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8623036
 
 gnomAD: MAF in the Latino population is 0.0006774 https://gnomad.broadinstitute.org/variant/17-45363789-G-A
 
 PreviouslyPublished: References 53-55
 
 CaseInfo Gene:ITGB3 Individual InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Zygosity:CompoundHeterozygous ProteinExpression:NotReported PlateletAggregation:NotReported PreviouslyPublished CAiD:CA8623036 inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
4. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 CW
 
 Case12: Patient CW (can be found in GT database) gender and age are not specified
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0031364, HP:0000979, HP:0000967, (Ecchymosis, Purpura/petechiae)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: <1% of normal GPIIIa and GPIIb surface expression
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.480C>G (p.Ser160_102del)
 
 LegacyVariant: N/A
 
 ClinVar: 2892 (Arg584Ter)
 
 CAiD: CA115834 and CA399805892
 
 gnomAD: MAF in the East Asian population is 0.0002176 for the Arg584Ter variant and MAF in the East Asian population is 0.00005507 for the other variant https://gnomad.broadinstitute.org/variant/17-42463013-G-C
 
 PreviouslyPublished: Reference number 23 in this article
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Mutation:Large Zygosity:CompoundHeterozygous ProteinExpression:Reported PlateletAggregation:NotReported PreviouslyPublished ClinVarID:2892 CAiD:CA115834 CAiD:CA399805892 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
5. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 NR
 
 Case19: Patient NR (found in the GT database as well) gender and age are not specified
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: Menorrhagia HP:0000132
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: N/A Undetectable
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.2941C>T
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399790399
 
 gnomAD: N/A
 
 PreviouslyPublished: Reference numbers 32,22 in this article
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA399790399 ProteinExpression:NotReported PlateletAggregation:NotReported PreviouslyPublished inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
6. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 17
 
 Case17: Patient MO (patient found in the GT database as well) gender and age are not specified here
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000978, HP:0000132 (Bruising, menorrhagia)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: N/A
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1750C>T (p.Arg584Ter)
 
 LegacyVariant: N/A
 
 ClinVar: 2892
 
 CAiD: CA115834
 
 gnomAD: MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A
 
 PreviouslyPublished: Reference numbers 29 and 30 in this article
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous ProteinExpression:NotReported PlateletAggregation:NotReported PreviouslyPublished ClinVarID:2892 CAiD:CA115834 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
7. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 LeM
 
 Case10: Patient LeM (found in the GT database) gender and age are not specified
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000979, HP:0000967 (Purpura/petechiae)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: <5% of normal expression
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1366_1371del
 
 LegacyVariant: N/A
 
 ClinVar: 2898
 
 CAiD: CA8603160
 
 gnomAD: MAF in the European (non-Finnish) population is 0.000008791 https://gnomad.broadinstitute.org/variant/17-42458268-TGTCTAC-T
 
 PreviouslyPublished: Reference number 21 in this article
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Large Zygosity:CompoundHeterozygous ProteinExpression:Reported PlateletAggregation:NotReported PreviouslyPublished ClinVarID:2898 CAiD:CA8603160 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
8. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 CG
 
 Case20: Patient CG (Found in GT database) also gender and age are not specified for this patient
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: Gingival bleeding and menorrhagia HP:0000225, HP:0000132
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: About 5% of normal GPIIIa and GPIIb surface expression
 
 PlateletAggregation: N/A
 
 CasePreviousTesting: N/A
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1787T>C and M_000419.3:c.3060+2T>C
 
 LegacyVariant: N/A
 
 ClinVar: 2900
 
 CAiD: CA115846 and CA290944108
 
 gnomAD: MAF in the European (non-Finnish) population is 0.0001325 https://gnomad.broadinstitute.org/variant/17-42457148-A-G and MAF in the European (non-Finnish) population is 0.00003876 https://gnomad.broadinstitute.org/variant/17-42451720-A-G
 
 PreviouslyPublished: References 34 and 35 in this article
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:2900 CAiD:CA115846 CAiD:CA290944108 ProteinExpression:Reported PlateletAggregation:NotReported PreviouslyPublished inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

InheritancePattern:NoInheritanceAssertion

CAiD:CA8623036

ClinVarID:2892

CAiD:CA8603160

CaseInfo

CAiD:CA115846

Mutation:Large

CAiD:CA115834

Mutation:Missense

CAiD:CA290944108

Individual

CAiD:CA399790399

CAiD:CA399805892

PreviouslyPublished

inferred_gene_hgnc:6138

ClinVarID:2900

inferred_gene_source:CAID

ClinVarID:2898

Mutation:Intronic

ClinGen ITGA2B/ITGB3

PlateletAggregation:NotReported

Mutation:Nonsense

Zygosity:CompoundHeterozygous

Gene:ITGA2B

ProteinExpression:NotReported

DiseaseEntity:GlanzmannThrombasthenia

inferred_gene_hgnc:6156

ProteinExpression:Reported

Gene:ITGB3

Annotators

ClingenBaseline

URL

reader.elsevier.com/reader/sd/pii/S1079979697901170
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Clinical and molecular insights into Glanzmann's thrombasthenia in China

11
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case30: GT30, Female, 13
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0000225, HP:0000132
 
 (Bruising, purpura, ecchymosis, epistaxis, gingival bleeding, menorrhagia)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.2330C>A (p.Ala777Asp) and NM_000419.3:c.2602-3C>G (no protein notation given)
 
 LegacyVariant: N/A
 
 ClinVar: 2893 (c.2602-3C>G)
 
 CAiD: CA399796685 (p.Ala777Asp) and CA10575472 (c.2602-3C>G)
 
 gnomAD: MAF for East Asian population: 0.00006523 https://gnomad.broadinstitute.org/variant/17-42453087-G-C
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Intronic Zygosity:CompoundHeterozygous PreviousTesting:Full PlateletAggregation:Reported ProteinExpression:Reported SupplementalData CAiD:CA399796685 CAiD:CA10575472 ClinVarID:2893 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case17a: GT17a, Female, 14 years old, sister of GT17b proband
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421
 
 (Bruising, purpura, ecchymosis, epistaxis)
 
 CaseHPOFreeText: Post traumatic hemorrhage
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed a small response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.799+2T>C and NM_000419.3:c.2671C>T (p.Gln891Ter)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399805155 (c.799 +2 T>C) and CA8602626 (p.Gln891Ter)
 
 gnomAD: N/A
 
 Individual CaseInfo Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399805155 CAiD:CA8602626 PreviousTesting:Full FamilyInfo ProteinExpression:Reported PlateletAggregation:Reported SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case35: GT35, Male, 1 year old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364
 
 (Bruising, purpura, ecchymosis)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.625-1G>A (c.625-1G>A) and NM_000419.3:c.659A>G (p.Tyr220Cys)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399805552 (c.625-1G>A) and CA399805484 (p.Tyr220Cys)
 
 gnomAD: MAF for (p.Tyr220Cys) in the South Asian population 0.00003266 https://gnomad.broadinstitute.org/variant/17-42462543-T-C
 
 Individual CaseInfo Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Intronic Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported SupplementalData CAiD:CA399805552 CAiD:CA399805484 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
4. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case26: GT26, Male, 13 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364
 
 (Bruising, purpura, ecchymosis)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.2333A>C (Gln778Pro) and NM_000419.3:c.2671C>T (p.Gln891Ter)
 
 LegacyVariant: N/A
 
 ClinVar: 225393 (p.Gln778Pro)
 
 CAiD: CA290947544 (p.Gln778Pro) and CA8602626 (p.Gln891Ter)
 
 gnomAD: MAF in East Asian population: 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported ClinVarID:225393 CAiD:CA290947544 CAiD:CA8602626 SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
5. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case41: GT41, Male, 5 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421
 
 (Bruising, purpura, ecchymosis, epistaxis)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.1736G>A (p.Trp579Ter) and NM_000212.2:c.1784_1802delinsGTCACA
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA400032429 (p.Trp579Ter) and CA915940255 (c.1784_1802delinsGTCACA)
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Mutation:Frameshift PreviousTesting:Full Zygosity:CompoundHeterozygous ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA400032429 CAiD:CA915940255 SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
6. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case8: GT8, Male, 9 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421
 
 (Bruising, purpura, ecchymosis, epistaxis)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1651C>T (p.Arg551Trp) and NM_000419.3:c.2236G>T (p.Glu746Ter)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399802348 (p.Arg551Trp) and CA399798321 (p.Glu746Ter)
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA399802348 CAiD:CA399798321 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
7. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case38: GT38, Female, 23 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000132
 
 (Bruising, purpura, ecchymosis, menorrhagia)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B and ITGB3
 
 Variant: NM_000419.3:c.2613del in ITGA2B (p.Leu872Cysfs*38) and NM_000212.2:c.1646G>C in ITGB3 (p.Cys549Ser)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA915940594 (p.Leu872Cysfs*38) and CA400030198 (p.Cys549Ser)
 
 gnomAD: MAF of (p.Cys549Ser) in the East Asian population: 0.00005453 https://gnomad.broadinstitute.org/variant/17-45369890-G-C
 
 CaseInfo Individual Gene:ITGA2B Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Frameshift Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported SupplementalData CAiD:CA915940594 CAiD:CA400030198 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
8. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case31: GT31, Female, 13 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0000225
 
 (Bruising, purpura, ecchymosis, epistaxis, gingival bleeding)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B and ITGB3
 
 Variant: NM_000419.3:c.1022C>T (p.Ala341Val) in ITGA2B and NM_000212.2:c.412G>A (p.Val138Met) in ITGB3
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399804629 (p.Ala341Val) and CA400021826 (p.Val139Met)
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA399804629 CAiD:CA400021826 SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
9. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case23: GT23, Female, 11 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0000225, HP:0000132
 
 (Bruising, purpura, ecchymosis, epistaxis, gingival bleeding, menorrhagia)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed a small response to ADP, no response to collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.1980C>A (p.Tyr660Ter) and NM_000212.2:c.2147G>T (p.Gly716Val)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA400032983 (p.Tyr660Ter) and CA400033923 (p.Gly716Val)
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA400032983 CAiD:CA400033923 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
10. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case40: GT40, Male, 5 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421
 
 (Bruising, purpura, ecchymosis, epistaxis)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.962G>T (p.Gly321Val)
 
 LegacyVariant: N/A
 
 ClinVar: 2892 (p.Arg584Ter)
 
 CAiD: CA115834 (p.Arg584Ter) and CA399804765 (p.Gly321Val)
 
 gnomAD: MAF for p.Arg584Ter in East Asian population 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported SupplementalData CAiD:CA115834 CAiD:CA399804765 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
11. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Tables 1 and 2 combined information:
 
 Case6: GT6, Male, 7 years old
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Not available per supplementary table 1
 
 ParentalGenotype: Parents are not consanguineous, no other genotype information available
 
 CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421
 
 (Bruising, purpura, ecchymosis, epistaxis)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry
 
 PlateletAggregation: Platelet aggregation showed a small amount of response to ADP and collagen but normal response to ristocetin
 
 CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.812C>G (p.Ala271Gly) and NM_000419.3:c.2172G>A (p.Met724Gln)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399805123 (p.Ala271Gly) and CA399798895 (p.Met724Gln)
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399805123 CAiD:CA399798895 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

InheritancePattern:NoInheritanceAssertion

CAiD:CA8602626

CAiD:CA399804629

PreviousTesting:Full

ClinVarID:2893

CAiD:CA399798895

CAiD:CA399798321

ClinVarID:225393

FamilyInfo

CaseInfo

CAiD:CA399796685

CAiD:CA115834

Mutation:Missense

CAiD:CA399805484

Individual

CAiD:CA400033923

CAiD:CA399805155

CAiD:CA399805123

inferred_gene_hgnc:6138

CAiD:CA399802348

CAiD:CA400021826

CAiD:CA915940594

inferred_gene_source:CAID

Mutation:Intronic

CAiD:CA290947544

CAiD:CA915940255

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

Zygosity:CompoundHeterozygous

Gene:ITGA2B

CAiD:CA399805552

DiseaseEntity:GlanzmannThrombasthenia

CAiD:CA400032429

CAiD:CA400030198

CAiD:CA10575472

CAiD:CA399804765

inferred_gene_hgnc:6156

ProteinExpression:Reported

Mutation:Frameshift

CAiD:CA400032983

SupplementalData

PlateletAggregation:Reported

Gene:ITGB3

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC6041146/
Local file Local file

untitled

2
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  GT23
  
  Case33: (GT23) Gender, age and ethnicity are not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Both brothers are heterozygous for this mutation and sister is normal
  
  ParentalGenotype: Father is heterozygous for the NM_000419.3:c.800-2A>T mutation and mother does not harbor this mutation. Mother is heterozygous for the NM_000419.3:c.1210+4A>G mutation and father does not have this mutation.
  
  CasePresentingHPOs:
  
  CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
  
  CaseNotHPOs: N/A
  
  ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
  
  Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
  
  CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.800-2A>T and NM_000419.3:c.1210+4A>G
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399805150 and CA915940692
  
  gnomAD N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive Mutation:Intronic Zygosity:CompoundHeterozygous CAiD:CA399805150 CAiD:CA915940692 PreviousTesting:Full FamilyInfo ParentalTesting:FullPhase ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  18
  
  Case2: GT18, Gender, age, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: 1 brother is heterozygous for the g.951G>A promoter variant and does not have the other Leu343Pro mutation and one brother is normal and does not have the NM_000419.3:c.2915dup mutation
  
  ParentalGenotype: Father: homozygous for the g.951G>A promoter variant and the Leu343Pro Mother: is heterozyous for both those mutations and mother does not have NM_000419.3:c.2915dup while the father is heterozygous for NM_000419.3:c.2915dup
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
  
  CaseNotHPOs: N/A
  
  ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
  
  Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
  
  CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
  
  Gene: ITGA2B
  
  Variant: NC_000017.11:g.44393555C>T (g.951G>A promoter variant) and NM_000419.3:c.1028T>C (p.Leu343Pro) and NM_000419.3:c.2915dup
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA913189168 (promoter variant) and CA399804619 (p.Leu343Pro) and CA8602531
  
  gnomAD MAF in the East Asian population is 0.0001088 https://gnomad.broadinstitute.org/variant/17-42452054-C-CG for the NM_000419.3:c.2915dup variant
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:PromoterVariant Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA913189168 CAiD:CA399804619 PreviousTesting:Full ParentalTesting:FullPhase FamilyInfo ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation CAiD:CA8602531 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

inferred_gene_hgnc:6138

CAiD:CA399805150

PreviousTesting:Full

ProteinExpression:MinimalInformation

inferred_gene_source:CAID

CAiD:CA399804619

Mutation:Intronic

FamilyInfo

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

PlateletAggregation:MinimalInformation

Individual

Mutation:PromoterVariant

CAiD:CA8602531

CAiD:CA915940692

CAiD:CA913189168

Annotators

ClingenBaseline
www.sciencedirect.com www.sciencedirect.com

A novel approach using ancillary tests to guide treatment of Glanzmann thrombasthenia patients undergoing surgical procedures

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  4
  
  Case2: 9 years old, Female, Jewish Iraqi
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0004406
  
  (Recurrent epistaxis)
  
  CaseHPOFreeText: Mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients demonstrated lack of αIIbβ3 surface expression." No specifics are given on the percentage, but test was performed
  
  PlateletAggregation: Presented with mucocutaneous bleeding, absence of platelet aggregation in response to all physiological agonists in contrast to normal aggregation with ristocetin
  
  CasePreviousTesting: "Molecular analysis disclosed that patient 2 was homozygous for an out of frame mutation (c.2031–2041 del, exon 13) in ITGB3, and patient 4 was compound heterozygote for the same deletion and a large deletion of 11.2Kb del"
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs) and 11.2Kb del (IVS9aluc.2183–6)
  
  LegacyVariant: N/A
  
  ClinVar: N/A and 13563
  
  CAiD: CA915940605 and NA
  
  gnomAD: N/A
  
  Individual CaseInfo Gene:ITGB3 InheritancePattern:NoInheritanceAssertion PlateletAggregation:Reported ProteinExpression:MinimalInformation Zygosity:CompoundHeterozygous Mutation:Frameshift Mutation:Large ClinVarID:13563 CAiD:CA915940605 inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

InheritancePattern:NoInheritanceAssertion

CAiD:CA915940605

ProteinExpression:MinimalInformation

Individual

inferred_gene_source:CAID

CaseInfo

inferred_gene_hgnc:6156

ClinVarID:13563

ClinGen ITGA2B/ITGB3

Mutation:Frameshift

Zygosity:CompoundHeterozygous

PlateletAggregation:Reported

Mutation:Large

Gene:ITGB3

Annotators

ClingenBaseline

URL

sciencedirect.com/science/article/pii/S107997961830247X
www.ahajournals.org www.ahajournals.org

atvb_atvb-2019-313191_supp1.pdf

3
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  GT10
  
  Case#: 2 year old, male
  
  Disease: Glazmann's Thrombasthenia
  
  CasePresentingHPOs: HP:0000967, HP:0000978, HP:0004406, HP:0006298, HP:0001892
  
  PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.
  
  GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing
  
  Allele 1:
  
  ClinVar: 1330345
  
  CAID: CA399805484
  
  Variant: NM_000419.5:c.659A>G
  
  GnomAD: South Asian at rate of 0.00003266 (1/30614)
  
  Allele 2:
  
  ClinVar:
  
  CAID:
  
  Variant:
  
  GnomAD:
  
  ExpressionEvidence: Flow Cytometry of platelet integrin: 99.9% B3 expression, 16.6% A2B expression
  
  Zygosity:Compoundheterozygous Individual Gene:ITGA2B CAID:CA399805484 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  GT9
  
  Case#: 13 year old, male
  
  Disease: Glazmann's Thrombasthenia
  
  CasePresentingHPOs: HP:0000967, HP:0000978, HP:0004406, HP:0000225, HP:0006298, HP:0001892, HP:0002239
  
  PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.
  
  GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing
  
  Allele 1:
  
  ClinVar: 996212
  
  CAID: CA399803786
  
  Variant: NM_000419.5:c.1229C>G
  
  GnomAD: European non-Finnish at rate of 0.0000089411 (1/111846)
  
  Allele 2:
  
  ClinVar: 225393
  
  CAID: CA290947544
  
  Variant: NM_000419.5:c.2333A>C
  
  GnomAD: East Asian population at rate of 0.0001087 (2/18394)
  
  ExpressionEvidence: Flow Cytometry of platelet integrin: 92.9% B3 expression, 2.1% A2B expression
  
  Gene:ITGA2B Individual CaseInfo Zygosity:Compoundheterozygous CAID:CA290947544 CAID:CA399803786 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  GT12
  
  Case#: 7 year old, female
  
  Disease: Glazmann's Thrombasthenia
  
  CasePresentingHPOs: HP:0000967, HP:0000978, HP:0000225, HP:0004406, HP:0006298, HP:0001892
  
  PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.
  
  GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing
  
  Allele 1:
  
  ClinVar: 2892
  
  CAID: CA115834
  
  Variant: NM_000419.5:c.1750C>T
  
  GnomAD: East Asian Population 0.0002176 (4/18386)
  
  Allele 2:
  
  ClinVar: 225393
  
  CAID: CA290947544
  
  Variant: NM_000419.5:c.2333A>C
  
  GnomAD: East Asian at a rate of 0.0001087 (2/18394)
  
  ExpressionEvidence:Flow Cytometry of platelet integrin: 94.9% B3 expression, 5.66% A2B expression
  
  Zygosity:Compoundheterozygous Individual CaseInfo CAID:CA115834 CAID:CA290947544 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

inferred_gene_hgnc:6138

CAID:CA399805484

CAID:CA115834

inferred_gene_source:CAID

CAID:CA399803786

ClinGen ITGA2B/ITGB3

CaseInfo

Gene:ITGA2B

Zygosity:Compoundheterozygous

Individual

CAID:CA290947544

Annotators

ClingenBaseline

URL

ahajournals.org/action/downloadSupplement
ashpublications.org ashpublications.org

A Leu262Pro mutation in the integrin β3 subunit results in an αIIb-β3 complex that binds fibrin but not fibrinogen

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Patient LD
  
  Case1: (Patient LD) Female, 3 years old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: See Fig 4 for family pedigree
  
  ParentalGenotype: Father is heterozygous for GC867-G and Mother is heterozygous for T882C (See Fig 4)
  
  CasePresentingHPOs: HP:0000967, HP:0031364, HP:0000978, HP:0000225
  
  (Petechiae, ecchymosis, bruising, gingival bleeding)
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Fig 2A shows reduced expression (See Fig2A)
  
  PlateletAggregation: Platelets did not aggregate in response to ADP, epinephrine, or arachidonic acid and showed only shape change in response to collagen. Platelets did agglutinate with ristocetin.
  
  CasePreviousTesting: Genomic DNA was prepared from peripheral blood leukocytes and amplified by polymerase chain reaction (PCR) with Taq polymerase by using oligonucleotide primers from intronic flanking sequences of αIIb and β3. All exons of both genes were sequenced at least twice to exclude Taq errors.
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.863T>C (p.Leu288Pro) and NM_000212.2:c.847_848del
  
  LegacyVariant: (p.Leu262Pro)
  
  ClinVar: N/A
  
  CAiD: CA400024958 and CA8623068
  
  gnomAD: for c.847_848del https://gnomad.broadinstitute.org/variant/17-45364504-AGC-A
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Frameshift Zygosity:CompoundHeterozygous FamilyInfo ParentalTesting:FullPhase ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA400024958 CAiD:CA8623068 inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

CAiD:CA8623068

inferred_gene_source:CAID

FamilyInfo

CAiD:CA400024958

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

Individual

inferred_gene_hgnc:6156

ProteinExpression:Reported

Mutation:Frameshift

PlateletAggregation:Reported

Gene:ITGB3

Annotators

ClingenBaseline

URL

ashpublications.org/blood/article/96/1/161/257783/A-Leu262Pro-mutation-in-the-integrin-3-subunit
www.thieme-connect.com www.thieme-connect.com

Glanzmannâs Thrombasthenia: Identification of 19 New Mutations in 30 Patients

7
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Case10: Patient PL, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: See Table 1
  
  PlateletAggregation: See Table 1
  
  CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1742C>A (p.Ala581Asp)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399802112
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA399802112 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Case6: Patient FF, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: See Table 1
  
  PlateletAggregation: See Table 1
  
  CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.855dup
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA915940766
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Insertion Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA915940766 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Case18: Patient ME, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: See Table 1
  
  PlateletAggregation: See Table 1
  
  CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2929C>T (p.Arg977Ter)
  
  LegacyVariant: (p.Arg946Ter)
  
  ClinVar: N/A
  
  CAiD: CA8602528
  
  gnomAD: MAF in the South Asian population is 0.00003266 https://gnomad.broadinstitute.org/variant/17-42452041-G-A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA8602528 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
4. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Case13: Patient BM, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: See Table 1
  
  PlateletAggregation: See Table 1
  
  CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2113T>C (p.Cys705Arg)
  
  LegacyVariant: (p.Arg674Arg)
  
  ClinVar: N/A
  
  CAiD: CA8602816
  
  gnomAD: MAF in the European (non-Finnish) population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA8602816 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
5. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Case19: Patient SM, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: See Table 1
  
  PlateletAggregation: See Table 1
  
  CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.355C>T and NM_000212.2:c.1801T>C
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA8622924 and CA8623361
  
  gnomAD: MAF in the South Asian population is 0.0001307 https://gnomad.broadinstitute.org/variant/17-45360909-C-T and MAF in the European non Finnish pop is 0.00001758 https://gnomad.broadinstitute.org/variant/17-45376784-T-C
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA8622924 CAiD:CA8623361 inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
6. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Case5: Patient DRP, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: See Table 1
  
  PlateletAggregation: See Table 1
  
  CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
  
  Gene: ITGA2B
  
  Variant: This variant has a typo in the paper the real variant is this: NM_000419.3:c.800 G>A and NM_000419.3:c.2930del
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399805147 and CA915940386
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA399805147 CAiD:CA915940386 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
7. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Case20: Patient LPR, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: See Table 1
  
  PlateletAggregation: See Table 1
  
  CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.355C>T and NM_000212.2:c.355C>T
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA8622924 and CA8623361
  
  gnomAD: MAF in the South Asian population is 0.0001307 https://gnomad.broadinstitute.org/variant/17-45360909-C-T and MAF in the European non Finnish pop is 0.00001758 https://gnomad.broadinstitute.org/variant/17-45376784-T-C
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA8622924 CAiD:CA8623361 inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

Mutation:Insertion

InheritancePattern:NoInheritanceAssertion

CAiD:CA8622924

PreviousTesting:Full

CAiD:CA915940386

CAiD:CA8602528

CaseInfo

Mutation:Missense

CAiD:CA399805147

Individual

CAiD:CA915940766

inferred_gene_hgnc:6138

CAiD:CA8623361

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

Zygosity:CompoundHeterozygous

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

CAiD:CA399802112

CAiD:CA8602816

inferred_gene_hgnc:6156

ProteinExpression:Reported

PlateletAggregation:Reported

Gene:ITGB3

Annotators

ClingenBaseline

URL

thieme-connect.com/products/ejournals/pdf/10.1055/s-0037-1613129.pdf
Local file Local file

untitled

5
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 2CabGT-2
 
 Case2: (Proband CabGT-2), Female, age not specified, European Caucasian
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 ProteinExpression: N/A
 
 Platelet Aggregation: N/A
 
 CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.917dup (p.Arg307GlufsTer22) and NM_000419.3:c.1912dup (p.Cys639MetfsTer22)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA290954352 (p.Arg307GlufsTer22) and CA915940678 (p.Cys639MetfsTer22)
 
 gnomAD N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Frameshift Zygosity:CompoundHeterozygous CAiD:CA290954352 ProteinExpression:NotReported PlateletAggregation:NotReported CAiD:CA915940678 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 26CabGT-26
 
 Case26: (Proband CabGT-26), Female, age not specified, North American
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 ProteinExpression: Flow cytometry showed 12% of both GPIIIa and GPIIb surface expression
 
 Platelet Aggregation: N/A
 
 CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
 
 Gene: ITGB3
 
 Variant: "c.1143C>A" is incorrect in the CAR- so will need a senior biocurator to ask-- and NM_000212.2:c.1260G>A
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8623200
 
 gnomAD MA in the African population is 0.00004005 https://gnomad.broadinstitute.org/variant/17-45368454-G-A
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Zygosity:CompoundHeterozygous CAiD:CA8623200 ProteinExpression:Reported PlateletAggregation:NotReported inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 25CabGT-25
 
 Case25: (Proband CabGT-25), Gender, age and ethnicity not specified
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 ProteinExpression: N/A
 
 Platelet Aggregation: N/A
 
 CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
 
 Gene: ITGB3
 
 Variant: c.112513_112516del (Not showing up in the CAR) and they could not determine the second variant
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: N/A
 
 gnomAD N/A
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion Mutation:Intronic DiseaseEntity:GlanzmannThrombasthenia Zygosity:CompoundHeterozygous UnregisteredVariant ProteinExpression:NotReported PlateletAggregation:NotReported inferred_gene_hgnc:6156 inferred_gene_source:Gene_Name ClinGen ITGA2B/ITGB3
4. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 6CabGT-6
 
 Case6: (Proband, CabGT-6), Male, age not specified, Caucasian
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 ProteinExpression: Flow cytometry showed <5% surface expression of GPIIIa and GPIIb
 
 Platelet Aggregation: N/A
 
 CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1413C>G (p.Tyr471Ter) and NM_000419.3:c.2800G>T (p.Val934Phe)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA290950376 (p.Tyr471Ter) and CA290946484 (p.Val934Phe)
 
 gnomAD MAF in the European (non-Finnish) population is 0.000008791 https://gnomad.broadinstitute.org/variant/17-42457994-G-C
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA290950376 CAiD:CA290946484 ProteinExpression:Reported PlateletAggregation:NotReported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
5. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 12
 
 Case12: (Proband CabGT-12), Female, age not specified, Caucasian
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 ProteinExpression: Flow cytometry showed 19% GPIIb and 40% GPIIIa surface expression
 
 Platelet Aggregation: N/A
 
 CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.2113T>C (p.Cys705Arg) and NM_000419.3:c.3060+2T>C (p.Val982_Lys1020del)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8602816 and CA290944108
 
 gnomAD MAF in the European (non-Finnish) population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G and MAF in the European non Finnish population for (p.Val982_Lys1020del) is 0.00003876 https://gnomad.broadinstitute.org/variant/17-42451720-A-G
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Large Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA8602816 CAiD:CA290944108 ProteinExpression:Reported PlateletAggregation:NotReported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

InheritancePattern:NoInheritanceAssertion

UnregisteredVariant

CAiD:CA290946484

CaseInfo

Mutation:Large

CAiD:CA290950376

Mutation:Missense

CAiD:CA290944108

Individual

CAiD:CA8623200

inferred_gene_hgnc:6138

inferred_gene_source:CAID

Mutation:Intronic

ClinGen ITGA2B/ITGB3

PlateletAggregation:NotReported

Mutation:Nonsense

Zygosity:CompoundHeterozygous

Gene:ITGA2B

ProteinExpression:NotReported

CAiD:CA290954352

DiseaseEntity:GlanzmannThrombasthenia

inferred_gene_source:Gene_Name

CAiD:CA915940678

CAiD:CA8602816

inferred_gene_hgnc:6156

ProteinExpression:Reported

Mutation:Frameshift

Gene:ITGB3

Annotators

ClingenBaseline
www.tandfonline.com www.tandfonline.com

A novel amino acid substitution of integrin αIIb in Glanzmann thrombasthenia confirms that the N-terminal region of the receptor plays a role in maintaining β-propeller structure

3
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  GT1
  
  Case1: GT-1, Female, Catalan, age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Affected sister (GT-1) and brother (GT-3)
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0000421
  
  (Epistaxis)
  
  CaseHPOFreeText: Hemorrhage associated with deciduous tooth loss
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Standard glycoprotein analysis confirmed the absence of αIIbβ3 in their platelets but while western blotting failed to reveal αIIb, residual β3 was at about 10% of usual levels and of normal migration (illustrated for GT1 in supplemental Figure 1).
  
  PlateletAggregation: Platelets of all 3 patients failed to aggregate in response to a range of physiologic agonists but were agglutinated by ristocetin. Clot retraction was also defective.
  
  CasePreviousTesting: Screened ITGA2B and ITGB3 genes of all three probands. Direct sequencing of all coding regions and splice sites of ITGA2B (30 exons) showed mutation.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.131G>T and NM_000419.3:c.1440-13_1440-1del
  
  LegacyVariant: (p.Gly13Val)
  
  ClinVar: N/A
  
  CAiD: CA399806881 and CA913184940
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Large Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399806881 CAiD:CA913184940 FamilyInfo ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  GT3
  
  Case3: GT-3, Male, Catalan, age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Affected sisters (GT-1) and (GT-2)
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0000421
  
  (Epistaxis)
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Standard glycoprotein analysis confirmed the absence of αIIbβ3 in their platelets but while western blotting failed to reveal αIIb, residual β3 was at about 10% of usual levels and of normal migration (illustrated for GT1 in supplemental Figure 1).
  
  PlateletAggregation: Platelets of all 3 patients failed to aggregate in response to a range of physiologic agonists but were agglutinated by ristocetin. Clot retraction was also defective.
  
  CasePreviousTesting: Screened ITGA2B and ITGB3 genes of all three probands. Direct sequencing of all coding regions and splice sites of ITGA2B (30 exons) showed mutation.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.131G>T and NM_000419.3:c.1440-13_1440-1del
  
  LegacyVariant: (p.Gly13Val)
  
  ClinVar: N/A
  
  CAiD: CA399806881 and CA913184940
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399806881 CAiD:CA913184940 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported FamilyInfo inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  GT2
  
  Case2: GT-2, Female, Catalan, age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Affected sister (GT-1) and brother (GT-3)
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0011891
  
  (Post-partum hemorrhage)
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs:
  
  CaseNotHPOsFreeText:
  
  ProteinExpression: Standard glycoprotein analysis confirmed the absence of αIIbβ3 in their platelets but while western blotting failed to reveal αIIb, residual β3 was at about 10% of usual levels and of normal migration (illustrated for GT1 in supplemental Figure 1).
  
  PlateletAggregation: Platelets of all 3 patients failed to aggregate in response to a range of physiologic agonists but were agglutinated by ristocetin. Clot retraction was also defective.
  
  CasePreviousTesting: Screened ITGA2B and ITGB3 genes of all three probands. Direct sequencing of all coding regions and splice sites of ITGA2B (30 exons) showed mutation.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.131G>T and NM_000419.3:c.1440-13_1440-1del
  
  LegacyVariant: (p.Gly13Val)
  
  ClinVar: N/A
  
  CAiD: CA399806881 and CA913184940
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399806881 CAiD:CA913184940 PreviousTesting:Full FamilyInfo ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

PreviousTesting:Full

CAiD:CA913184940

inferred_gene_source:CAID

FamilyInfo

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

Mutation:Large

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

Individual

CAiD:CA399806881

ProteinExpression:Reported

PlateletAggregation:Reported

Annotators

ClingenBaseline

URL

tandfonline.com/doi/full/10.3109/09537104.2012.665278
Local file Local file

untitled

3
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  GT 26
  
  Case7: GT26, Female, India, age of onset is 4 years old
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: N/A
  
  PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
  
  CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2929_2930del (p.Glu979SerfsTer28)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA915940726
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA915940726 PreviousTesting:Full ProteinExpression:NotReported PlateletAggregation:Reported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  GT 04
  
  Case15: GT04, Female, India, age of onset is 11 years old
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: Menorrhagia HP:0000132
  
  CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: N/A
  
  PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
  
  CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.356G>A (p.Arg119Gln)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA400020703 and CA8622925
  
  gnomAD: MAF in the Other population is 0.0001385 https://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the African population is 0.0002470 https://gnomad.broadinstitute.org/variant/17-45360910-G-A
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full CAiD:CA400020703 CAiD:CA8622925 ProteinExpression:NotReported PlateletAggregation:Reported inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  GT 09
  
  Case18: GT09, Female, India, age of onset is 21 years old
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: N/A
  
  PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
  
  CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.428T>G (p.Leu143Trp) and NM_000212.2:c.1261G>A (p.Val422Met)
  
  LegacyVariant: N/A
  
  ClinVar: 13567
  
  CAiD: CA123252 and CA400028437
  
  gnomAD: MAF in the Other population is 0.0001629 https://gnomad.broadinstitute.org/variant/17-45361875-T-G
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:13567 CAiD:CA123252 CAiD:CA400028437 PreviousTesting:Full PlateletAggregation:Reported ProteinExpression:NotReported inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

PreviousTesting:Full

inferred_gene_source:CAID

CAiD:CA400020703

CAiD:CA400028437

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

ProteinExpression:NotReported

ClinVarID:13567

DiseaseEntity:GlanzmannThrombasthenia

CAiD:CA915940726

Mutation:Missense

Individual

inferred_gene_hgnc:6156

CAiD:CA8622925

PlateletAggregation:Reported

CAiD:CA123252

Gene:ITGB3

Annotators

ClingenBaseline
Local file Local file

Tanaka_et_al-2002-British_Journal_of_Haematology.pdf

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  The patient
  
  Case1: Female, 21 years old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Blood samples collected from brother, no other information provided
  
  ParentalGenotype: Father heterozygous: NM_000419.3:c.258G>C and mother heterozygous: NM_000419.3:c.2334A>C
  
  CasePresentingHPOs: HP:0000421, HP:0000979
  
  (Epistaxis, purpura)
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry analysis and western blot analysis showed a remarkable reduction in aIIb b3 and aIIb, and a moderate reduction in b3 in the platelets of the patient (data not shown)
  
  PlteletAggregation: N/A
  
  CasePreviousTesting: Nucleotide sequences of aIIb cDNA and b3 cDNA amplified by reverse transcription polymerase chain reaction (RT-PCR) were analyzed
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.258G>C (p.Leu86Pro) and NM_000419.3:c.2334A>C
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA500624524 and CA399796662
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA915940226 CAiD:CA399796662 PreviousTesting:Full ProteinExpression:Reported FamilyInfo:Minimal InheritancePattern:AutosomalRecessive ParentalTesting:FullPhase PlateletAggregation:NotReported inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

PreviousTesting:Full

FamilyInfo:Minimal

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

PlateletAggregation:NotReported

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

CAiD:CA399796662

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

Individual

inferred_gene_hgnc:6156

ProteinExpression:Reported

CAiD:CA915940226

Annotators

ClingenBaseline
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Glanzmann thrombasthenia in Pakistan: molecular analysis and identification of novel mutations

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  A
  
  Case1: Patient ID A, Male, 6 years old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A (Parents are consangenous)
  
  CasePresentingHPOs: HP:0000978, HP:0002239
  
  (Easy bruising, gastrointestinal bleeding)
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: HP:0000967, HP:0000979, HP:0004406, HP:0000225, HP:0002239, HP:0000790, HP:0005261
  
  (Petechiae, purpura, recurrent epistaxis, gingival bleeding, intracranial hemorrhage, hematuria, hemarthrosis)
  
  CaseNotHPOsFreeText: Hemhorrage after dental, hemhorrage after trauma, ear bleeding, hematoma
  
  ProteinExpression: N/A
  
  PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin
  
  CasePreviousTesting: Exon PCR was used to amplify a;; coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.435C>A (p.Asn145Lys) and NM_000419.3:c.531T>A (p.Cys177Ter)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399805991 and CA290955739
  
  gnomAD: N/A
  
  PreviouslyPublished: PMID: 20020534
  
  CaseInfo Individual InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous PreviousTesting:Full PlateletAggregation:Reported ProteinExpression:NotReported CAiD:CA399805991 CAiD:CA290955739 Gene:ITGA2B PreviouslyPublished inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

PreviousTesting:Full

CAiD:CA290955739

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

ProteinExpression:NotReported

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

Individual

CAiD:CA399805991

PlateletAggregation:Reported

PreviouslyPublished

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC4737203/
Local file Local file

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort

16
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case14: GT15, Female, 35, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0031364, HP:0000967, HP:0000421, HP:0000225
 
 (Ecchymosis, petechiae, epistaxis, gingival bleeding)
 
 CaseHPOFreeText: Bleeding from birth and hematomas from excersize
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% variant expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.2095-19T>A and NM_000419.3:c.2770C>T (p.Gln924Ter)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA915940312 and CA399792054
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA915940312 CAiD:CA399792054 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case28: GT33a, Male, age not specified, USA/Laos
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Affected sister who is proband 33b in this article
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0002239
 
 (Epistaxis, GI bleeding)
 
 CaseHPOFreeText: Life-threatening bleeding at onset of menses
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.2113del (p.Leu705Cysfs*4)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA400020703 and CA8623443
 
 gnomAD: MAF in the Other population is 0.0001385 http://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Frameshift Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA400020703 CAiD:CA8623443 PreviousTesting:Full FamilyInfo:Minimal ProteinExpression:Reported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case15: GT18, Male, 20, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0031364, HP:0000978
 
 (Ecchymosis, easy bruising)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed 10% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Residual platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1201G>T (pGly401Cys) andNM_000419.3:c.2800G>T (p.Val934Phe)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399804280 and CA290946484
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399804280 CAiD:CA915940226 PreviousTesting:Full PlateletAggregation:MinimalInformation ProteinExpression:Reported SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
4. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case31: GT35a, Female, 18 years old, USA
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Affected sister who is 35 b in this study (See Supplementary Table S1)
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0002239
 
 (Epistaxis, GI bleeding)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B and ITGB3
 
 Variant: ITGB3: NM_000212.2:c.392G>C (p.Arg131Pro) and NM_000212.2:c.777+1G>A ITGA2B: NM_000419.3:c.2264G>A (p.Arg755Gln)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8622954, CA8623036, CA8602771
 
 gnomAD: MAF in the African population is 0.00006152 http://gnomad.broadinstitute.org/variant/17-45361839-G-C, MAF in the Latino population is 0.0006774 http://gnomad.broadinstitute.org/variant/17-45363789-G-A, MAF in the Latino population is 0.0001903 http://gnomad.broadinstitute.org/variant/17-42454380-C-T
 
 CaseInfo Individual Gene:ITGA2B Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Intronic Zygosity:CompoundHeterozygous CAiD:CA8622954 CAiD:CA8623036 CAiD:CA8602771 PreviousTesting:Full FamilyInfo:Minimal PreviousTesting:Partial ProteinExpression:Reported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
5. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case53: GT53, Male, 16 years old, Argentenian/Brazilian
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421
 
 (Epistaxis)
 
 CaseHPOFreeText: Hematomas
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.356G>A (p.Gly201Ser) and NM_000212.2:c.1697G>A (p.Arg119Gln)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8622925 and CA400032338
 
 gnomAD: MAF in the African population is http://gnomad.broadinstitute.org/variant/17-45360910-G-A
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD: CA400032338 CAiD:CA8622925 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
6. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case46: GT45, Male, 86 years old, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0000225, HP:0002239
 
 (Epistaxis, gingival bleeding, GI bleeding)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.551_626del (p.Arg184_Gln208del) and LR deletion
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA915940373
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Large Zygosity:CompoundHeterozygous Mutation:MinimalInformation PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation CAiD:CA915940373 SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
7. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case48: GT48, Male, 10 years old, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0031364, HP:0000421, HP:0001934
 
 (Ecchymosis, epistaxis, persistent bleeding after trauma)
 
 CaseHPOFreeText: Frequent hematomas
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: No serious episode of spontaneous bleeding
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: N/A (Not available for this proband see Supp Table S1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.1094A>G (p.Asn365Ter) and NM_000212.2:c.1522del (p.Gln508Serfs*161)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA400026292 and CA772541579
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGB3 DiseaseEntity:GlanzmannThrombasthenia InheritancePattern:NoInheritanceAssertion Mutation:Frameshift Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported CAiD:CA400026292 CAiD:CA772541579 PlateletAggregation:NotReported SupplementalData Mutation:Nonsense inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
8. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case19: GT22, Male, 13, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000978, HP:0000225
 
 (Easy bruising, gingival bleeding)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.408+11C>A and NM_000419.3:c.1259T>C (p.Val420Ala)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA915940333 and CA399803733
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA915940333 CAiD:CA399803733 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
9. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case64: GT67, Male, 61 years old, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Affected brother who is now dead (this is all the information we are provided with)
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs:
 
 (Gingival bleeding, epistaxis, bleeding after dental extraction )
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.1618C>T (p.Gln540Ter)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA913184940 and CA399802411
 
 gnomAD: MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42457504-G-A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA913184940 CAiD:CA399802411 PreviousTesting:Full FamilyInfo:Minimal ProteinExpression:Reported PlateletAggregation:Reported SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
10. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case27: GT31, Female, 13, USA
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000225, HP:0000421
 
 (Gingival bleeding and epistaxis)
 
 CaseHPOFreeText: Life-threatening bleeding at onset of menses
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed 5-10% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1771dup (p.Asp591Glyfs*47) and NM_000419.3:c.3061-1G>A
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA915940334 and CA399787972
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Frameshift Mutation:Intronic Zygosity:CompoundHeterozygous CAiD:CA915940334 CAiD:CA399787972 PreviousTesting:Full PlateletAggregation:MinimalInformation ProteinExpression:Reported SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
11. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case44: GT43b, Male, 11 years old, Morrocan
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: Affected sister is 43a (See Supplementary Table S1)
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0000979, HP:0031364, HP:0000967, HP:0030137
 
 (Epistaxis, purpura, ecchymosis, petechiae, prolonged bleeding at circumcision)
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.614+1G>T and NM_000212.2:c.683G>A (p.Arg228His)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA400023344 and CA8623025
 
 gnomAD: MAF in the African population is 0.00008012 http://gnomad.broadinstitute.org/variant/17-45363694-G-A
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Intronic Zygosity:CompoundHeterozygous CAiD:CA400023344 CAiD:CA8623025 PreviousTesting:Full FamilyInfo:Minimal ProteinExpression:Reported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
12. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case56: GT57, Female, 10, Argentinian/European
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0000967
 
 (Epistaxis, petechia)
 
 CaseHPOFreeText: Hematomas
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.571T>G (p.Phe191Val) and NM_000419.3:c.961G>T (p.Phe191Alafs*32)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399805699 and CA399804768
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA399805699 CAiD:CA399804768 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
13. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case62: GT65, Female, 31 years old, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0000790, HP:0002239, HP:0006298
 
 (Epistaxis, gingival bleeding, menorrhagia, hematuria, GI bleeding, bleeding after dental procedure)
 
 CaseHPOFreeText: Tonsil bleeding, muscle hematomas
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.574+1G>A and NM_000419.3:c.1946+3G>T
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399805691 and CA626121071
 
 gnomAD: MAF in the European (non-Finnish) population is 0.00001235 https://gnomad.broadinstitute.org/variant/17-42462918-C-T and MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42456008-C-A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Zygosity:CompoundHeterozygous CAiD:CA399805691 CAiD:CA626121071 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
14. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case13: GT14, Female, 10, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000979 and HP:0006298
 
 (Purpura, prolonged bleeding after dental extraction)
 
 CaseHPOFreeText: Moderate cutaneous bleeding from birth
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% variant expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.423G>T (p.Trp141Cys) and NM_000419.3:c.2902del (p.Tyr968Metfs*163)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399806022 and CA915940332
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:SingleNucleotideDeletion Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation CAiD:CA399806022 CAiD:CA915940332 SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
15. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case51: GT51, Male, 29 years old, French/African
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0000421 (Epistaxis)
 
 CaseHPOFreeText: Mucocutaneous bleeding
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: N/A
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGB3
 
 Variant: NM_000212.2:c.861del (p.Arg287Serfs * 34) and NM_000212.2:c.1456del (p.Cys486Alafs * 183)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA915940375 and CA915940376
 
 gnomAD: N/A
 
 CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Zygosity:CompoundHeterozygous PreviousTesting:Full PlateletAggregation:MinimalInformation ProteinExpression:NotReported CAiD:CA915940375 CAiD:CA915940376 SupplementalData Mutation:Frameshift inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
16. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplementary Table S1 & S2 Proband and Variant Information:
 
 Case22: GT25, Male, 81, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: HP:0002239
 
 Gastrointestinal bleeding
 
 CaseHPOFreeText: Life-long bleeding disorder
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
 
 PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
 
 CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1413C>G (p.Tyr471Ter) and NM_000419.3:c.1882C>T (p.Arg628Ter)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA290950376 and CA399801310
 
 gnomAD: MAF in the European (non-Finnish) population 0.000008791 http://gnomad.broadinstitute.org/variant/17-42457994-G-C and MAF in Latino population is 0.00003983 http://gnomad.broadinstitute.org/variant/17-42456075-G-A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA290950376 CAiD:CA399801310 PreviousTesting:Full ProteinExpression:Reported ProteinExpression:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

CAiD:CA400023344

InheritancePattern:NoInheritanceAssertion

CAiD:CA8623036

CAiD:CA399805691

PreviousTesting:Full

ProteinExpression:MinimalInformation

CAiD:CA913184940

CAiD:CA399805699

Mutation:SingleNucleotideDeletion

CaseInfo

CAiD:CA8623025

Mutation:Large

CAiD:CA290950376

Mutation:Missense

Individual

CAiD:CA915940334

CAiD:CA8602771

CAiD:CA399803733

CAiD:CA915940375

inferred_gene_hgnc:6138

CAiD:CA915940312

CAiD:CA915940373

FamilyInfo:Minimal

CAiD:CA399806022

inferred_gene_source:CAID

CAiD:CA400020703

Mutation:Intronic

PlateletAggregation:Reported

CAiD:CA915940376

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

PreviousTesting:Partial

PlateletAggregation:NotReported

CAiD:CA399801310

Zygosity:CompoundHeterozygous

CAiD:CA400026292

CAiD:CA399802411

CAiD:CA399804280

Gene:ITGA2B

CAiD:CA8622954

CAiD:CA772541579

Mutation:MinimalInformation

DiseaseEntity:GlanzmannThrombasthenia

CAiD:CA399787972

ProteinExpression:NotReported

CAiD:CA8623443

PlateletAggregation:MinimalInformation

CAiD:CA915940332

CAiD:CA399792054

CAiD: CA400032338

CAiD:CA626121071

inferred_gene_hgnc:6156

CAiD:CA8622925

ProteinExpression:Reported

Mutation:Frameshift

CAiD:CA399804768

SupplementalData

CAiD:CA915940333

CAiD:CA915940226

Gene:ITGB3

Annotators

ClingenBaseline
instructure-uploads.s3.amazonaws.com instructure-uploads.s3.amazonaws.com

Revista 6-2 jul-dec 2007.p65

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Patient TK
  
  Case1: (Patient TK) Male, 5 years old, Japanese
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: The (p.His280Pro) mutation was inherited from his mother and the (p.Gly579Ser) mutation was inherited from his father
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients (3 in this study) had suffered from a bleeding diathesis since early childhood
  
  CaseNotHPOs: NA
  
  ProteinExpression: The surface expression of the alphaIIbbeta complex on the patients' platelets was quantitated by flow cytometry. The level of antigen expression for TK was 19.9%
  
  Platelet Aggregation: Absent platelet aggregation in response to ADP, collagen, and epinephrine, but normal platelet agglutination in response to ristocetin
  
  CasePreviousTesting: The nucleotide sequences of the aIIb and b3 coding regions were determined by direct sequencing of RT-PCR products from platelet RNA
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.917A>C (p.His206Pro) and NM_000212.2:c.1813G>A (p.Gly605Ser) (See Table 1 to see zygosity statement, "double heterozygote for both variants")
  
  LegacyVariant: (p.His280Pro) and (p.Gly579Ser)
  
  ClinVar: N/A
  
  CAiD: CA291224999 and CA291227621
  
  gnomAD MAF in the East Asian population for (p.His206Pro) is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45364575-A-C and MAF in East Asian population for (p.Gly605Ser) is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45376796-G-A
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense CAiD:CA291224999 CAiD:CA291227621 PreviousTesting:Full ParentalTesting:FullPhase ProteinExpression:Reported PlateletAggregation:Reported Zygosity:CompoundHeterozygous inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

PreviousTesting:Full

CAiD:CA291224999

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CAiD:CA291227621

CaseInfo

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

Individual

inferred_gene_hgnc:6156

ProteinExpression:Reported

PlateletAggregation:Reported

Gene:ITGB3

Annotators

ClingenBaseline

URL

instructure-uploads.s3.amazonaws.com/account_32860000000000001/attachments/2737386/Inoki et al 2002.pdf
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Functional and molecular characterization of inherited platelet disorders in the Iberian Peninsula: results from a collaborative study

2
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Table 3 Molecular Diagnosis of Patients with Glanzmann Thrombasthenia:
  
  Case1: GT-1, age, gender, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type II
  
  FamilyInfo: Segregation analysis confirmed in presence of heterozygous mutations in this proband.
  
  ParentalGenotype: Although segregation analysis confirmed, we do not know which variant in particular came from mom or dad.
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Patients presented with a variable bleeding diathesis; most patients had epistaxis (54%), cutaneous bleeding (58%), and menorrhagia (100% of women) while other common symptoms (oral cavity, GI, following dental extraction of mild injuries, postpartum, or hematomas) were in general milder. There is no specific phenotypes attached to probands in this paper.
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry showed that αIIbβ3 expression was between 5% and 20%
  
  PlateletAggregation: There was severely impaired aggregation in response to all physiological agonists, and ristocetin induced platelet agglutination was normal or reduced to some extent.
  
  CasePreviousTesting: Total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Then, using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing. Every mutation found in cDNA was confirmed in DNA samples.
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.448A>G (p.Met124Val) and NM_000212.2:c.774_775del (p.Cys258Ter)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA8622961 and CA915940285
  
  gnomAD: MAF in South Asian population is 0.00003266 http://gnomad.broadinstitute.org/variant/17-45361895-A-G
  
  CaseInfo Individual Gene:ITGB3 Zygosity:CompoundHeterozygous Mutation:Nonsense Mutation:Missense InheritancePattern:AutosomalRecessive CAiD:CA8622961 CAiD:CA915940285 PreviousTesting:Full FamilyInfo ProteinExpression:Reported PlateletAggregation:Reported ParentalTesting:MinimalInfo inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Table 3 Molecular Diagnosis of Patients with Glanzmann Thrombasthenia:
  
  Case2: GT-2, age, gender, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: Segregation analysis confirmed in presence of heterozygous mutations in this proband.
  
  ParentalGenotype: Although segregation analysis confirmed, we do not know which variant in particular came from mom or dad.
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Patients presented with a variable bleeding diathesis; most patients had epistaxis (54%), cutaneous bleeding (58%), and menorrhagia (100% of women) while other common symptoms (oral cavity, GI, following dental extraction of mild injuries, postpartum, or hematomas) were in general milder. There is no specific phenotypes attached to probands in this paper.
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry showed that αIIbβ3 expression was less than 5%
  
  PlateletAggregation: There was severely impaired aggregation in response to all physiological agonists, and ristocetin induced platelet agglutination was normal or reduced to some extent.
  
  CasePreviousTesting: Total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Then, using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing. Every mutation found in cDNA was confirmed in DNA samples.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2473_2481delinsTCACCTGGTC and NM_000419.3:c.641T>C (p.Leu214Pro)
  
  LegacyVariant: p.Leu183Pro
  
  ClinVar: (p.Leu214Pro is 2901)
  
  CAiD: CA915940289 and CA115848
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Missense Mutation:Large CAiD:CA915940289 CAiD:CA115848 PreviousTesting:Full ParentalTesting:MinimalInfo FamilyInfo:Minimal ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

inferred_gene_hgnc:6138

Gene:ITGB3

PreviousTesting:Full

FamilyInfo:Minimal

inferred_gene_source:CAID

FamilyInfo

Mutation:Nonsense

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

Mutation:Large

Gene:ITGA2B

Mutation:Missense

ParentalTesting:MinimalInfo

InheritancePattern:AutosomalRecessive

Individual

inferred_gene_hgnc:6156

CAiD:CA115848

CAiD:CA915940285

ProteinExpression:Reported

PlateletAggregation:Reported

CAiD:CA915940289

CAiD:CA8622961

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC4302577/
Local file Local file

REV_ISS_WEB_BJH_14283_175-4 686..695

13
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case28: GT33a, USA/Laos, gender and age not specified or reported
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.2113del (p.Ley705Cysfs*4)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA400020703 and CA8623443
  
  gnomAD: MAF in the Other population is 0.0001385 for (p.Arg88Ter) https://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the East Asian population is 0.0001087 for (p.Ley705Cysfs*4) https://gnomad.broadinstitute.org/variant/17-45380183-TC-T
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Mutation:Frameshift Zygosity:CompoundHeterozygous CAiD:CA400020703 CAiD:CA8623443 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case6: GT7, French, gender and age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.187C>T (p.Arg63Cys) and NM_000212.2:c.505C>T (p.Arg169Ter)
  
  LegacyVariant: N/A
  
  ClinVar: 631774
  
  CAiD: CA8622892 and CA291224658
  
  gnomAD: MAF in the East Asian population is 0.00005012 https://gnomad.broadinstitute.org/variant/17-45360741-C-T
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA8622892 CAiD:CA291224658 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case55: GT65, French, gender and age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.574+1G>A and NM_000419.3:c.1946+3G>T
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399805691 and CA626121071
  
  gnomAD: MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42456008-C-A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Zygosity:CompoundHeterozygous CAiD:CA399805691 CAiD:CA626121071 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
4. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case13: GT14, French, gender age and ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.423G>T (p.Trp141Cys) and NM_000419.3:c.2902del (p.Tyr968Metfs*163)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399806022 and CA915940332
  
  gnomAD: N/A
  
  ClinGen General Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Frameshift Zygosity:CompoundHeterozygous CAiD:CA399806022 CAiD:CA915940332 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
5. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case9: French/Italian, gender and age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.3077G>A (p.Arg1026Gln)
  
  LegacyVariant: N/A
  
  ClinVar: 50232
  
  CAiD: CA913184940 and CA10575572
  
  gnomAD: MAF in the European (non-Finnish) population is 0.000008801 https://gnomad.broadinstitute.org/variant/17-42449775-C-T for (p.Arg1026Gln)
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Frameshift Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA913184940 CAiD:CA10575572 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
6. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case49: GT57, Argentinian/European, gender and age are not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.571T>G (p.Phe191Ala/ p.Phe191AlafsTer32) and NM_000419.3:c.961G>T (p.Gly321Trp)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399805699 and CA399804768
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399804768 CAiD:CA399805699 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
7. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case8: GT9, French, gender and age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.665T>C (p.Leu222Pro) and NM_000212.2:c.1871G>A (p.Cys624Tyr)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA291224887 and CA400032726
  
  gnomAD: MAF in the European (non-Finnish) population is 0.00006482 https://gnomad.broadinstitute.org/variant/17-45363676-T-C
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA291224887 CAiD:CA400032726 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
8. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case18: GT21, French, gender and age are not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs106) and NM_000419.3:c.2864T>A
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA913184940 and CA399791171
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Large Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA913184940 CAiD:CA399791171 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
9. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case29: GT34, USA, gender and age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1553T>A (p.Ile518Asn) and NM_000419.3:c.1946+3G>T
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA8603038 and CA626121071
  
  gnomAD: MAF in the European (non-Finnish) population is 0.000008790 https://gnomad.broadinstitute.org/variant/17-42457661-A-T and MAF in the African population for NM_000419.3:c.1946+3G>T is 0.000 https://gnomad.broadinstitute.org/variant/17-42456008-C-A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Intronic Zygosity:CompoundHeterozygous CAiD:CA8603038 CAiD:CA626121071 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
10. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case14: GT15, French, gender and age are not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2095-19T>A and NM_000419.3:c.2770C>T
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA915940312 and CA399792054
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA915940312 CAiD:CA399792054 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
11. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case35: GT41a, Canadian/Chinese, gender and age not specified here
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.91del (p.Ala31ProfsTer2) and NM_000419.3:c.2915dup (p.Leu973AlafsTer63)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA913203486 and CA8602531
  
  gnomAD: MAF in the East Asian population is 0.0001088 https://gnomad.broadinstitute.org/variant/17-42452054-C-CG for the variant (p.Leu973Alafs*63)
  
  CaseInfo Individual InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Mutation:Frameshift Zygosity:CompoundHeterozygous CAiD:CA913203486 CAiD:CA8602531 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData Gene:ITGA2B inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
12. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case31: GT36a, Spain, gender and age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.131G>T (p.Gly44Val) and NM_000419.3:c.1440-13_1440-1del
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399806881 and CA913184940
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Large Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399806881 CAiD:CA913184940 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
13. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Supplementary Table S1:
  
  Case39: GT45, French, age and gender not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia type I
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
  
  PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
  
  CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.551_626del (p.Arg184_Gln208del) and the other variant is noted as "LR deletion" and that is all the information we are given so I will note it as an Unknown Variant
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA915940373
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Large VariantUnknown CAiD:CA915940373 Zygosity:CompoundHeterozygous PreviousTesting:Full ProteinExpression:NotReported PlateletAggregation:MinimalInformation SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

InheritancePattern:NoInheritanceAssertion

CAiD:CA399805691

PreviousTesting:Full

ProteinExpression:MinimalInformation

CAiD:CA913184940

CAiD:CA399805699

CAiD:CA8603038

CAiD:CA8622892

CaseInfo

Mutation:Large

ClinGen

Mutation:Missense

Individual

CAiD:CA399806881

CAiD:CA913203486

General

inferred_gene_hgnc:6138

CAiD:CA915940312

CAiD:CA915940373

CAiD:CA399806022

inferred_gene_source:CAID

CAiD:CA400020703

Mutation:Intronic

CAiD:CA10575572

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

Zygosity:CompoundHeterozygous

CAiD:CA399791171

Gene:ITGA2B

ProteinExpression:NotReported

CAiD:CA400032726

DiseaseEntity:GlanzmannThrombasthenia

CAiD:CA8623443

CAiD:CA291224658

PlateletAggregation:MinimalInformation

CAiD:CA915940332

CAiD:CA626121071

CAiD:CA291224887

CAiD:CA399792054

inferred_gene_hgnc:6156

CAiD:CA8602531

VariantUnknown

CAiD:CA399804768

Mutation:Frameshift

SupplementalData

Gene:ITGB3

Annotators

ClingenBaseline
onlinelibrary.wiley.com onlinelibrary.wiley.com

HAE_2744 201..209

1
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 GT8
 
 Case8: (GT-8) Female, 10 years old, French
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: Mucocutaneous bleeding
 
 CaseNotHPOs: N/A
 
 ProteinExpression: <5% surface expression levels of αIIbβ3
 
 Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)
 
 CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.682C>T (p.Gln228Ter) and NM_000419.3:c.1750C>T (p.Arg584Ter)
 
 LegacyVariant: (p.Gln197Ter) and (p.Arg558Ter) (The paper gives legacy and current nomenclature)
 
 ClinVar: 2892 (p.Arg584Ter)
 
 CAiD: CA399805421 (p.Gln228Ter) CA115834 (p.Arg584Ter)
 
 gnomAD MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Zygosity:CompoundHeterozygous ClinVarID:2892 CAiD:CA399805421 CAiD:CA115834 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

PreviousTesting:Full

ClinVarID:2892

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

CAiD:CA115834

DiseaseEntity:GlanzmannThrombasthenia

CAiD:CA399805421

PlateletAggregation:MinimalInformation

Individual

ProteinExpression:Reported

Annotators

ClingenBaseline

URL

onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2516.2011.02744.x
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Two novel ITGA2B mutations in a Glanzmann thrombasthaenia family associated with different platelet phenotypic expression

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  The proband is a 35-day old female infant born from a twin delivery.
  
  Case1: Female, 35 day old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: The proband’s mother and father carry heterozygous c.512delC and c.1686delG mutations, respectively. Other parameters for parents are shown in Table 1.
  
  CasePresentingHPOs: HP:0031364, HP:0000967
  
  (Ecchymosis, petechiae)
  
  CaseHPOFreeText: Large parietal and cervical cephalohaematoma, severe anemia
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry of platelet surface antigens revealed the absence of the αIIbβ3 complex.
  
  PlateletAggregation: Prolonged closure time at PFA-100, absent ADP, adrenaline, collagen induced platelet aggregation, and ristocetin induced platelet aggregation at the lower limit of normal
  
  CasePreviousTesting: Sequencing of ITGA2B and ITGB3 genes showed that proband is compound het.
  
  Gene: ITGA2B
  
  Variant: Can not conclusively determine if c.481delC and c.1654delG are the variants intended by the authors based on the available information.
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: N/A
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:Frameshift Zygosity:CompoundHeterozygous PreviousTesting:Full ParentalTesting:FullPhase ProteinExpression:Reported PlateletAggregation:Reported VariantUnknown inferred_gene_hgnc:6138 inferred_gene_source:Gene_Name ClinGen ITGA2B/ITGB3
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Tags

inferred_gene_hgnc:6138

DiseaseEntity:GlanzmannThrombasthenia

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

inferred_gene_source:Gene_Name

PreviousTesting:Full

VariantUnknown

Individual

PlateletAggregation:Reported

ClinGen ITGA2B/ITGB3

ProteinExpression:Reported

Mutation:Frameshift

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC5589712/
www.ahajournals.org www.ahajournals.org

Two Types of Procoagulant Platelets Are Formed Upon Physiological Activation and Are Controlled by Integrin αIIbβ3 | Arteriosclerosis, Thrombosis, and Vascular Biology

1
1. ClingenBaseline 23 Oct 2026
  
  in Baseline Annotations
  
  patient (GT-1
  
  Case1: GT-1, gender, age, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Relatively mild bleeding syndrome and does not routinely require treatment except for iron supplementation
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry showed that this patient lacked integrin αIIbβ3 expression
  
  PlateletAggregation: Platelets failed to aggregate with physical agonists
  
  CasePreviousTesting: N/A
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2933G>T (p.Gly978Val) and NM_000419.3:c.2994G>A (p.Trp998Ter)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399790478 and CA399789759
  
  gnomAD: N/A
  
  CaseInfo Individual InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Mutation:Nonsense Zygosity:CompoundHeterozygous ProteinExpression:Reported PlateletAggregation:Reported Gene:ITGA2B CAiD:CA399790478 CAiD:CA399789759 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

inferred_gene_hgnc:6138

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

InheritancePattern:NoInheritanceAssertion

CAiD:CA399790478

Individual

PlateletAggregation:Reported

CAiD:CA399789759

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

ProteinExpression:Reported

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

Annotators

ClingenBaseline

URL

ahajournals.org/doi/full/10.1161/ATVBAHA.112.253765
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

GDAP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia

1
1. ClingenBaseline 23 Oct 2026
 
 in Baseline Annotations
 
 Patient NIJ
 
 MonDO: MONDO:0032706
 
 Case: Patient NIJ. 46 year old Dutch/Egyptian female onset of gait difficulties at age 34 with progressive worsening. Analysis of the maternal DNA revealed that she carries the p.Gln316* mutation, but not the frameshift mutation, indicating that the mutations in the proband are on opposite alleles.
 
 DiseaseAssertion: Cerebellar ataxia
 
 FamilyInfo:
 
 CasePresentingHPOs: HP:0001288, HP:0007979, HP:0008003, HP:0007338, HP:0001251, HP:0002064, HP:0006895, HP:0001348 (Gait disturbance, Gaze-evoked horizontal nystagmus, Jerky ocular pursuit movements, Hypermetric saccades, Ataxia, Spastic gait, Lower limb hypertonia, Brisk reflexes
 
 CaseHPOFreeText: Difficulty writing, cerebellar dysarthria, downgoing plantar responses, ataxia on finger chase and heel-shin slide, Mild spastic paraplegia Cervical dystonia
 
 CasePreviousTesting: No weakness. Normal sensory examination. An MRI brain scan revealed mild cerebellar atrophy. Ophthalmological examinations were normal. Nerve conduction studies and EMG did not show evidence of a peripheral neuropathy. Laboratory testing including vitamin E, metabolic screening, albumin, cholesterol, alpha-fetoprotein, lactate, acanthocytes, copper, ceruloplasmin, and coeliac screen was normal or negative. Genetic testing for Friedreich, spinocerebellar ataxias (SCAs) 1, 2, 3, 6, 12, 14 and 17, dentatorubral-pallidoluysian atrophy, autosomal recessive spastic ataxia of Charlevoix-Saguenay and SPG7 were negative.
 
 GenotypingMethod: Exome sequencing. Sanger sequencing was performed for confirmation of the variants and for segregation analyses using standard techniques. Altogether, 117 708 variants (single nucleotide variants and small deletions/insertions/indels) were detected. Initial filtering for a gene panel of movement disorders revealed no mutations.Variants were filtered for variant type, rarirty (MAF <0.5%) and conservation (>0.75, phyloP). Paternal DNA unavailable.
 
 MultipleGeneVariants:
 
 (1) GeneName: GDAP2
 
 (1) Variant: c.946C>T; p.(Gln316*)
 
 (1) ClinVarID or CAID: CA1031513
 
 (1) gnomAD: Total AF 0.00006711 (gnomAD v4.1, https://gnomad.broadinstitute.org/variant/1-117896840-G-A?dataset=gnomad_r4)
 
 (2) GeneName: GDAP2
 
 (2) Variant: c.1305dup p.(Ser436fs*36)
 
 (2) ClinVarID or CAID: CA913189981
 
 (2) gnomAD: Total AF 0.000001301, gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-117878149-A-AC?dataset=gnomad_r4)
 
 CaseInfo MONDO:0032706 Zygosity:CompoundHeterozygous inferred_gene_hgnc:18010 inferred_gene_source:CAID UNC Biocuration Core
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Tags

UNC Biocuration Core

MONDO:0032706

Zygosity:CompoundHeterozygous

inferred_gene_hgnc:18010

CaseInfo

inferred_gene_source:CAID

Annotators

ClingenBaseline

URL

pmc.ncbi.nlm.nih.gov/articles/PMC7534050/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

blt-16-392.pdf

1
1. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 37-year old woman
 
 Case1: Female patient, 37-year-old, At age 25(pregnant) an F8 mutation was identified, Family History of Severe HA
 
 DiseaseAssertion: Mild hemophilia A due to a family mutation and de novo mutation
 
 FamilyInfo: Family also has the large deletion of exon 1 to 22 of the F8 gene, Son (age 10) has mild Hemophilia A
 
 ParentalTesting: Father tested negative for any F8 mutations, Mother is an asymptomatic carrier of the familial large deletion
 
 CasePresentingHPOs: HP:0000978 (Bruising Susceptibility), HP:0000132 (Menorrhagia)
 
 CaseHPOFreeText: FVIII:C 7%, compounded heterozygous for the large gene deletion and c.1569G>T mild mutation
 
 CasePreviousTesting: Molecular analysis, Sequenced the whole coding region of the F8 gene
 
 Gene: F8
 
 Variant: 1. F8, EX1-22DEL 2. NM_000132.3:c.1569G>T (p.Leu523=)
 
 ClinVar: 1. 10122 https://www.ncbi.nlm.nih.gov/clinvar/variation/10122/
 
 439678 https://www.ncbi.nlm.nih.gov/clinvar/variation/439678/
 
 gnomAD: 1. Not reported (F8, EX1-22DEL)
 
 MAF for Leu523= in Latino population 0.00007293 https://gnomad.broadinstitute.org/variant/X-154185415-C-A?dataset=gnomad_r2_1
 
 CaseInfo Gene:F8 HGNC:3546 DiseaseEntity:FactorVIIIDeficiency InheritancePattern:Xlinked InheritancePattern:DeNovoAssertion Mutation:Large Zygosity:CompoundHeterozygous ClinVarID:10122 ClinVarID:439678 FVIIItesting:Partial ParentalTest:Both ParentalConfirmation:Paternity Mutation:Synonymous inferred_gene_hgnc:3546 inferred_gene_source:hgnc_tag ClinGen Coag Fac Def VCEP
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Tags

InheritancePattern:DeNovoAssertion

InheritancePattern:Xlinked

ClinVarID:439678

inferred_gene_source:hgnc_tag

ClinVarID:10122

Mutation:Synonymous

ParentalTest:Both

DiseaseEntity:FactorVIIIDeficiency

Zygosity:CompoundHeterozygous

CaseInfo

Mutation:Large

inferred_gene_hgnc:3546

FVIIItesting:Partial

HGNC:3546

ParentalConfirmation:Paternity

Gene:F8

ClinGen Coag Fac Def VCEP

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC6034774/
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study

3
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Table 2.
  
  Case#:Not assigned
  
  DiseaseAssertion:MPS type I with evidence of cognitive impairment defined as a score of at least 1 SD below mean on IQ testing or in one domain of neuropsychological function; attenuated MPS I
  
  FamilyInfo:No information
  
  CasePresentingHPOs:HP:0100543
  
  CaseHPOFreeText:
  
  CaseNotHPOs:HP:0032557
  
  CaseNotHPOFreeText:Subjects were excluded if they had undergone hematopoietic stem cell transplantation, were unable to comply with study procedures, had significant lumbar pathology precluding access to the intrathecal space via lumbar puncture, or significantly impaired spinal CSF flow as detected on a nuclear medicine flow study as part of screening.
  
  CaseEnzymeAssay:No information
  
  CaseUrineGAGs:No information
  
  CaseERT:Yes
  
  CaseBMT:No (exclusion criterion)
  
  Variant1:L238Q
  
  Variant1ClinVarID:
  
  Variant1CAID:
  
  Variant2:W402X
  
  Variant2ClinVarID:
  
  Variant2CAID:
  
  AdditionalVariants:N/A
  
  ParentalGenotype:Not specified
  
  PreviouslyPublished
  
  Gene:IDUA PMCID:PMC7813548 Zygosity:CompoundHeterozygous DiseaseEntity:MPS1 inferred_gene_hgnc:5391 inferred_gene_source:Gene_Name IDUA variant annotation
2. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Table 2.
  
  Case#:Not assigned
  
  DiseaseAssertion:MPS type I with evidence of cognitive impairment defined as a score of at least 1 SD below mean on IQ testing or in one domain of neuropsychological function; attenuated MPS I
  
  FamilyInfo:No information
  
  CasePresentingHPOs:HP:0100543
  
  CaseHPOFreeText:
  
  CaseNotHPOs:HP:0032557
  
  CaseNotHPOFreeText:Subjects were excluded if they had undergone hematopoietic stem cell transplantation, were unable to comply with study procedures, had significant lumbar pathology precluding access to the intrathecal space via lumbar puncture, or significantly impaired spinal CSF flow as detected on a nuclear medicine flow study as part of screening.
  
  CaseEnzymeAssay:No information
  
  CaseUrineGAGs:No information
  
  CaseERT:Yes
  
  CaseBMT:No (exclusion criterion)
  
  Variant1:int3 425a>g
  
  Variant1ClinVarID:
  
  Variant1CAID:
  
  Variant2:int5 1487g>a
  
  Variant2ClinVarID:
  
  Variant2CAID:
  
  AdditionalVariants:N/A
  
  ParentalGenotype:Not specified
  
  PreviouslyPublished
  
  Gene:IDUA PMCID:PMC7813548 DiseaseEntity:MPS1 Zygosity:CompoundHeterozygous inferred_gene_hgnc:5391 inferred_gene_source:Gene_Name IDUA variant annotation
3. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Table 2.
  
  Case#:Not assigned
  
  DiseaseAssertion:MPS type I with evidence of cognitive impairment defined as a score of at least 1 SD below mean on IQ testing or in one domain of neuropsychological function; attenuated MPS I
  
  FamilyInfo:No information
  
  CasePresentingHPOs:HP:0100543
  
  CaseHPOFreeText:
  
  CaseNotHPOs:HP:0032557
  
  CaseNotHPOFreeText:Subjects were excluded if they had undergone hematopoietic stem cell transplantation, were unable to comply with study procedures, had significant lumbar pathology precluding access to the intrathecal space via lumbar puncture, or significantly impaired spinal CSF flow as detected on a nuclear medicine flow study as part of screening.
  
  CaseEnzymeAssay:No information
  
  CaseUrineGAGs:No information
  
  CaseERT:Yes
  
  CaseBMT:No (exclusion criterion)
  
  Variant1:W402X
  
  Variant1ClinVarID:
  
  Variant1CAID:
  
  Variant2:int11 -7c>t
  
  Variant2ClinVarID:
  
  Variant2CAID:
  
  AdditionalVariants:N/A
  
  ParentalGenotype:Not specified
  
  PreviouslyPublished
  
  Gene:IDUA PMCID:PMC7813548 DiseaseEntity:MPS1 Zygosity:CompoundHeterozygous inferred_gene_hgnc:5391 inferred_gene_source:Gene_Name IDUA variant annotation
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Tags

inferred_gene_source:Gene_Name

Gene:IDUA

PMCID:PMC7813548

inferred_gene_hgnc:5391

DiseaseEntity:MPS1

IDUA variant annotation

Zygosity:CompoundHeterozygous

Annotators

ClingenBaseline

URL

pmc.ncbi.nlm.nih.gov/articles/PMC7813548/
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Identification of infants at risk for developing Fabry, Pompe or Mucopolysaccharidosis-I from newborn blood spots by tandem mass spectrometry

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Three samples were confirmed to have nucleotide changes consistent with MPS-I (Table II).
  
  Case#:Table II, MPS-1, Enzyme activity=1.06*
  
  DiseaseAssertion: MPS1
  
  FamilyInfo:
  
  CasePresentingHPOs:
  
  CaseHPOFreeText:
  
  CaseNotHPOs:
  
  CaseNotHPOFreeText:
  
  CaseEnzymeAssay: 1.06 umol/hr/L blood, newborn blood spot
  
  CaseUrineGAGs:
  
  CaseERT:
  
  CaseBMT:
  
  Variant1:c.355G>T (p.Asp119Tyr)
  
  Variant1ClinVarID: 2432701
  
  Variant1CAID: CA2801882
  
  Variant2: c.250G>A (p.Gly84Ser)
  
  Variant2ClinVarID: 726495
  
  Variant2CAID: CA2801152
  
  AdditionalVariants:
  
  ParentalGenotype:
  
  PreviouslyPublished
  
  Gene:IDUA HGNC:5391 PMCID:PMC3725184 InheritancePattern:AutosomalRecessive DiseaseEntity:MPS1 Mutation:Germline Zygosity:CompoundHeterozygous ClinvarID: 243201 ClinvarID: 726495 inferred_gene_hgnc:5391 inferred_gene_source:hgnc_tag IDUA variant annotation
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Tags

ClinvarID: 243201

InheritancePattern:AutosomalRecessive

Gene:IDUA

Mutation:Germline

inferred_gene_source:hgnc_tag

inferred_gene_hgnc:5391

DiseaseEntity:MPS1

IDUA variant annotation

Zygosity:CompoundHeterozygous

PMCID:PMC3725184

ClinvarID: 726495

HGNC:5391

Annotators

ClingenBaseline

URL

pmc.ncbi.nlm.nih.gov/articles/PMC3725184/
www.annclinlabsci.org www.annclinlabsci.org

A Novel Case of Compound Heterozygous Type 3 Von Willebrand Disease

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  A Novel Case of Compound Heterozygous Type 3Von Willebrand Disease
  
  PMID: unknown
  
  Gene: VWF
  
  HGNCID: 12726
  
  Case: 2 year old female
  
  DiseaseAssertion: type 3 VWD
  
  FamilyInfo: 27 year old parents with no history of abnormal bleeding, non-consanguineous. Older brother (4 years old) with symptoms, younger brother asymptomatic.
  
  ParentalGenotype(s): Mother is heterozygous for c.2345del variant. Father is heterozygous for exon 6 deletion.
  
  CasePresentingHPOs: HP:0001934, HP:0000978, HP:0000225, HP:0001058, HP:0001058, HP:0012147, HP:0030132
  
  CaseHPOFreeRext: reduced VWF activity
  
  CaseNOTHPOs: HP:0001873, HP:0008151
  
  CaseNOTHPOFreeText: reduced factor VIII
  
  CasePreviousTesting: n/a
  
  GenotypingMethod: unknown
  
  PreviouslyPublished: n/a
  
  Gene: VWF
  
  Variant: compound heterozygous c2345delC in exon 18 and deletion in exon 6
  
  HGVS: NM_000552.5:c.2435del p. (Pro812ArgfsTer31)
  
  ClinVarID: 303
  
  CAID:
  
  gnomAD: 0.00007187 (11/1613916 alleles) https://gnomad.broadinstitute.org/variant/12-6044297-CG-C?dataset=gnomad_r4
  
  DiseaseEntity:VWD3 AlleleOrigin:Germline Mutation:Frameshift Zygosity:CompoundHeterozygous ClinVarID:303 FamilyInfo ParentalTest:FullPhase inferred_gene_hgnc:12726 inferred_gene_source:HGNC_body ClinGen VWF
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Tags

DiseaseEntity:VWD3

inferred_gene_source:HGNC_body

ClinVarID:303

inferred_gene_hgnc:12726

FamilyInfo

ClinGen VWF

Mutation:Frameshift

AlleleOrigin:Germline

Zygosity:CompoundHeterozygous

ParentalTest:FullPhase

Annotators

ClingenBaseline

URL

annclinlabsci.org/content/49/3/393.full.pdf
www.thieme-connect.com www.thieme-connect.com

10.1055/a-2616-5161

3
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  10 Type 2A c.3610C > T Nc.3839T > C Np.Arg1204Trpp.Phe1280Ser2728D3-E3A1htzhtzMissenseMissensena 26 14 34
  
  Case: 10 (also in (also in row 10 table 6)
  
  DiseaseAssertion: type 2A VWD
  
  FamilyInfo:
  
  ParentalGenotype(s):
  
  CasePresentingHPOs:
  
  CaseHPOFreeRext: VWF:Ag [IU/dL] = 26; VWF:Ac [IU/dL] = 14; FVIII:C [IU/dL] = 34
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText:
  
  CasePreviousTesting:
  
  GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.
  
  PreviouslyPublished:
  
  Gene: VWF
  
  Variant: c.3610C>T p.Arg1204Trp
  
  HGVS:
  
  ClinVarID: 2682106
  
  CAID:
  
  gnomAD: absent
  
  MultipleGeneVariants:
  
  Gene: VWF
  
  Variant: c.3839T>C p.Phe1280Ser
  
  CAID: CA383506874
  
  gonmAD: absent
  
  DiseaseEntity:VWD2A ClinVarID:2682106 Mutation:Missense InheritancePattern:NoInheritanceAssertion CAID:CA383506874 Zygosity:CompoundHeterozygous inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
2. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  7 Type 2A c.2546 þ 1G > A Nc.5092G > T Np.Gly1698Cys 1929D’A3htzhtzSplice SiteMissenseO 27 16 31
  
  Case: 7 (also in row 2 splice variants table 6)
  
  DiseaseAssertion: type 2A VWD
  
  FamilyInfo:
  
  ParentalGenotype(s):
  
  CasePresentingHPOs: HP:0032442 - blood group O
  
  CaseHPOFreeRext: VWF:Ag [IU/dL] = 27; VWF:Ac [IU/dL] = 16; FVIII:C [IU/dL] = 31
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText:
  
  CasePreviousTesting:
  
  GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.
  
  PreviouslyPublished:
  
  Gene: VWF
  
  Variant: c.2546+1G > A
  
  HGVS:
  
  ClinVarID: not found
  
  CAID: CA383520269
  
  gnomAD: 0.000001239 (2 in 1614166) no homozygotes https://gnomad.broadinstitute.org/variant/12-6036387-C-T?dataset=gnomad_r4
  
  MultipleGeneVariants:
  
  Gene: VWF
  
  Variant: c.5092G > T p.Gly1698Cys
  
  CAID: CA383496674
  
  gnomAD: 6.196e-7 (1 in 1613980) no homozygotes https://gnomad.broadinstitute.org/variant/chr12-6016832-C-A?dataset=gnomad_r4
  
  Mutation:Intronic CAID:CA383520269 DiseaseEntity:VWD2A InheritancePattern:NoInheritanceAssertion CAID:CA383496674 Zygosity:CompoundHeterozygous inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
3. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  8 Type 2A /2N c.2561G > Ac.4811T > A Np.Arg854Glnp.Val1604Asp2028D’-E’A2htzhtzMissenseMissenseA 16 8 12
  
  Case: 8 (also in row 21 table 6)
  
  DiseaseAssertion: type 2A/2N VWD
  
  FamilyInfo:
  
  ParentalGenotype(s):
  
  CasePresentingHPOs: HP:0032370 - blood group A
  
  CaseHPOFreeRext: VWF:Ag [IU/dL] = 16; VWF:Ac [IU/dL] = 8; FVIII:C [IU/dL] = 12
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText:
  
  CasePreviousTesting:
  
  GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.
  
  PreviouslyPublished:
  
  Gene: VWF
  
  Variant: c.2561G>A p.Arg854Gln
  
  HGVS:
  
  ClinVarID: 296
  
  CAID:
  
  gnomAD: 0.004956 (8000 in 1614214) 26 homozygotes https://gnomad.broadinstitute.org/variant/12-6034812-C-T?dataset=gnomad_r4
  
  MultipleGeneVariants:
  
  Gene: VWF
  
  Variant: c.4811T>A p.Val1604Asp
  
  CAID: CA383499144
  
  gnomAD: absent
  
  DiseaseEntity:VWD2A DiseaseEntity:VWD2N ClinVarID:296 Mutation:Missense InheritancePattern:NoInheritanceAssertion CAID:CA383499144 Zygosity:CompoundHeterozygous inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
Visit annotations in context

Tags

CAID:CA383520269

InheritancePattern:NoInheritanceAssertion

inferred_gene_source:CAID

Mutation:Intronic

CAID:CA383499144

CAID:CA383506874

DiseaseEntity:VWD2N

ClinGen VWF

CAID:CA383496674

Zygosity:CompoundHeterozygous

Mutation:Missense

DiseaseEntity:VWD2A

ClinVarID:296

inferred_gene_hgnc:12726

ClinVarID:2682106

Annotators

ClingenBaseline

URL

thieme-connect.com/products/ejournals/pdf/10.1055/a-2616-5161.pdf
watermark.silverchair.com watermark.silverchair.com

aqac126.035.pdf

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  A case report of type 2M Von Willebrand disease withunique mutations
  
  Gene: VWF
  
  HGNCID: 12726
  
  Case: 55 year old female
  
  DiseaseAssertion: type 2M VWD
  
  FamilyInfo: one sister with VWD of unknown type. Four other siblings with no bleeding history.
  
  CasePresentingHPOs: HP:0002239 (Gastrointestinal hemorrhage), Gastrointestinal angiodysplasia HP:0000471, Hemoptysis HP:0002105, Epistaxis HP:0000421, Menorrhagia HP:0000132
  
  CaseHPOFreeRext: normal PT/aPTT. Von Willebrand panel shows vWF antigen of 33%, VWF ristocetin cofactor activity of 15%, and Factor VIII of 87%. The ratio (VWF: RCo/VWF: Ag) is low (0.45) and the multimer pattern is normal.
  
  Gene: VWF
  
  Variant: c.4241T>G (p.Val1414Gly) and c.5227G>A (p.Val1743Met)
  
  ClinVarID: 619752, 801307
  
  DiseaseEntity:VWD2M Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:801307 ClinVarID:619752 inferred_gene_hgnc:12726 inferred_gene_source:HGNC_body ClinGen VWF
Visit annotations in context

Tags

Mutation:Missense

ClinVarID:619752

inferred_gene_source:HGNC_body

inferred_gene_hgnc:12726

ClinGen VWF

Zygosity:CompoundHeterozygous

ClinVarID:801307

DiseaseEntity:VWD2M

Annotators

ClingenBaseline

URL

watermark.silverchair.com/aqac126.035.pdf
ashpublications.org ashpublications.org

von Willebrand factor antigen levels are associated with burden of rare nonsynonymous variants in the VWF gene

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Cohort description
  
  Case#: MK0251
  
  DiseaseAssertion: Type 2 VWD
  
  CaseHPOFreeText: 51 year old, female, VWF:AG LEVELS = 60
  
  Gene: VWF
  
  Variant: compound heterozygous for 4751A>G (p.Y1584C) and c.7483del (p.Leu2495CysfsTer8) variants
  
  ClinVar: 310 (p.Y1584C) and 631687 (p.Leu2495CysfsTer8)
  
  gnomAD: absent grpmax (p.Leu2495CysfsTer8), grpmax of 0.004019 based on european non finnish pop (p.Y1584C)
  
  InheritancePattern:AutosomalRecessive DiseaseEntity:VWD2 Mutation:Frameshift Mutation:Missense ClinVar: 310 Clinvar: 631687 Zygosity:CompoundHeterozygous inferred_gene_hgnc:12726 inferred_gene_source:Gene_Name ClinGen VWF
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Tags

Mutation:Missense

InheritancePattern:AutosomalRecessive

inferred_gene_source:Gene_Name

ClinVar: 310

inferred_gene_hgnc:12726

ClinGen VWF

Mutation:Frameshift

Zygosity:CompoundHeterozygous

Clinvar: 631687

DiseaseEntity:VWD2

Annotators

ClingenBaseline

URL

ashpublications.org/blood/article/137/23/3277/475195/von-Willebrand-factor-antigen-levels-are
onlinelibrary.wiley.com onlinelibrary.wiley.com

Molecular characterization, recombinant protein expression, and mRNA analysis of type 3 von Willebrand disease: Studies of an Italian cohort of 10 patients

3
1. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 8 M/46 <1 7 No 19 c.4576C>Ta/c.6973T>Aa p.Q1526Xa/p.C2325Sa 28/40 Heterozygous
 
 Case: 8, M, 46, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (IU/dL): <1, FVIII:C (IU/dL): 7, Bleeding Score: 19
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 c.4576C>T (p.Gln1526X), Exon 28
 
 c.6973T>A (p.Cys2325Ser), Exon 40, B1 Domain
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 Zygosity:CompoundHeterozygous Mutation:Nonsense Mutation:Missense CAID:CA232297763 CAID:CA383488305 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
2. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 9 F/21 <1 3 No 26 c.1–30071_220+3445del/c.3940delGa p.M1_G74delX8/p.V1314SfsX33a 1–3/28 Heterozygous
 
 Case: 9, F, 21, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (IU/dL): <1, FVIII:C (IU/dL): 3, Bleeding Score: 26
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 c.1–30071_220+3445del (p.Met1_Gly74delX8), Exon 1-3
 
 c.3940delG (p.Val1314SerfsX33), Exon 28
 
 Compound Heterozygous
 
 DiseaseEntity:VWD3 Mutation:Inframe CAID:CA2499221796 Mutation:c.1–30071_220+3445del Zygosity:CompoundHeterozygous inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
3. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 6 M/28 <1 9 No 15 c.2157delA/c.7729+7C>T p.D720TfsX21/p.E2577GfsX21 16/(45) Heterozygous
 
 Case: 6, M, 28, Italian
 
 DiseaseAssertion: VWD type 3
 
 FamilyInfo: Consanguinity: no
 
 ParentalGenotype: n/a
 
 CasePresentingHPOs: n/a
 
 CaseHPOFreeText: VWF:Ag (IU/dL): <1, FVIII:C (IU/dL): 9, Bleeding Score: 15
 
 CaseNotHPOs: n/a
 
 CaseNotHPOFreeText: Anti-VWF alloantibodies: no
 
 CasePreviousTesting: n/a
 
 Gene: VWF
 
 Variant:
 
 c.2157delA (p.Asp20ThrfsX21), Exon 16
 
 c.7729+7C>T (p.Glu2577GlyfsX21), Intron 45
 
 Compound Heterozygous
 
 Note: patient also has homozygous deletion of 40 bp (NP_000543.2, where 1 is adenine in ATG initiation codon) due to the skipping of exon 50; c.7729+7C>T resulted in altering the normal mRNA splicing process
 
 DiseaseEntity:VWD3 Mutation:Frameshift Mutation:Intronic Zygosity:CompoundHeterozygous CAID:CA228312 CAID:CA228815 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
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Tags

DiseaseEntity:VWD3

inferred_gene_source:CAID

Mutation:Intronic

Mutation:Nonsense

ClinGen VWF

Mutation:c.1–30071_220+3445del

Zygosity:CompoundHeterozygous

Mutation:Missense

CAID:CA228815

CAID:CA232297763

inferred_gene_hgnc:12726

CAID:CA228312

Mutation:Frameshift

CAID:CA383488305

Mutation:Inframe

CAID:CA2499221796

Annotators

ClingenBaseline

URL

onlinelibrary.wiley.com/doi/10.1002/ajh.23265
onlinelibrary-wiley-com.libproxy.lib.unc.edu onlinelibrary-wiley-com.libproxy.lib.unc.edu

von Willebrand disease type1/type 2N compound heterozygotes: diagnostic and management challenges

4
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  2
  
  Case#: 2, female, 25yo
  
  DiseaseAssertion: VWD1
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0000978, HP:0000421, HP:0000132, HP:0011891, HP:0004846, HP:0012147 (bruising susceptibility, epistaxis, Menorrhagia, Post-partum hemorrhage, Reduced quantity of VWF, Impaired ristocetin cofactor assay activity)
  
  CaseHPOFreeText: Type A blood, VWF:Ag (0·55–2 iu/ml) pre = 0·48, VWF:RCo (0·55–2 iu/ml) pre = 0·53, FVIII:C (0·55–2 iu/ml) pre = 0·25, FVIII:C/VWF:Ag ratio = 0·52, VWF:FVIII binding (>20%) = N/A, VWF:FVIII binding/VWF:Ag (>0·7) = N/A, multiple surgical interventions with VWF concentrate with adequate haemostasis
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: N/A
  
  ProteinExpression: N/A
  
  CasePreviousTesting: RFLP; confirmatory sequencing
  
  Gene: VWF
  
  Variant 1: NM_000552.4(VWF):c.2561G>A (p.Arg854Gln)
  
  ClinVar: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/
  
  gnomAD: MAF = 0.005692 (European Non-Finnish); https://gnomad.broadinstitute.org/variant/12-6143978-C-T
  
  Variant 2: N/A - stated to be a compound heterozygote for a 2N VWD and a presumed null mutation
  
  Individual CaseInfo InheritancePattern:AutosomalRecessive DiseaseEntity:VWD1 Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:296 inferred_gene_hgnc:12726 inferred_gene_source:RefSeq ClinGen VWF
2. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  1
  
  Case#: 1, female, 44yo
  
  DiseaseAssertion: VWD1
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0007420, HP:0000132, HP:0004846, HP:0012147, HP:0030129, HP:0030130 (spontaneous hematomas, Menorrhagia, Reduced quantity of VWF, Impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity)
  
  CaseHPOFreeText: Type O blood, VWF:Ag (0·55–2 iu/ml) pre = 0·47, VWF:RCo (0·55–2 iu/ml) pre = 0·5, FVIII:C (0·55–2 iu/ml) pre = 0·16, FVIII:C/VWF:Ag ratio = 0·32, VWF:FVIII binding (>20%) = 7%, VWF:FVIII binding/VWF:Ag (>0·7) = 0·15, patient died after motor vehicle accident
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: N/A
  
  ProteinExpression: N/A
  
  CasePreviousTesting: RFLP; confirmatory sequencing
  
  Gene: VWF
  
  Variant 1: NM_000552.4(VWF):c.2561G>A (p.Arg854Gln)
  
  ClinVar: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/
  
  gnomAD: MAF = 0.005692 (European Non-Finnish); https://gnomad.broadinstitute.org/variant/12-6143978-C-T
  
  Variant 2: N/A - stated to be a compound heterozygote for a 2N VWD and a presumed null mutation
  
  Individual CaseInfo InheritancePattern:AutosomalRecessive DiseaseEntity:VWD1 Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:296 inferred_gene_hgnc:12726 inferred_gene_source:RefSeq ClinGen VWF
3. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  3
  
  Case#: 3, female, 19yo
  
  DiseaseAssertion: VWD1
  
  FamilyInfo: brother diagnosed with VWD
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0000978; HP:0000132, HP:0004846, HP:0012147, HP:0030129 (Bruising susceptibility, Menorrhagia, Reduced quantity of VWF, Impaired ristocetin cofactor assay activity)
  
  CaseHPOFreeText: Type O blood, VWF:Ag (0·55–2 iu/ml) pre = 0·14, VWF:RCo (0·55–2 iu/ml) pre = 0·15, FVIII:C (0·55–2 iu/ml) pre = 0·1, FVIII:C/VWF:Ag ratio = 0·71, VWF:FVIII binding (>20%) = n/a, VWF:FVIII binding/VWF:Ag (>0·7) = n/a, spinal surgery with VWF concentrate and adequate haemostasis
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: N/A
  
  ProteinExpression: N/A
  
  CasePreviousTesting: RFLP; confirmatory sequencing
  
  Gene: VWF
  
  Variant 1: NM_000552.4(VWF):c.2561G>A (p.Arg854Gln)
  
  ClinVar: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/
  
  gnomAD: MAF = 0.005692 (European Non-Finnish); https://gnomad.broadinstitute.org/variant/12-6143978-C-T
  
  Variant 2: N/A - stated to be a compound heterozygote for a 2N VWD and a presumed null mutation
  
  Individual CaseInfo InheritancePattern:AutosomalRecessive DiseaseEntity:VWD1 Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:296 inferred_gene_hgnc:12726 inferred_gene_source:RefSeq ClinGen VWF
4. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  4
  
  Case#: 4, male, 23yo
  
  DiseaseAssertion: VWD1
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0004846, HP:0012147, HP:0030129 (Reduced quantity of VWF, Impaired ristocetin cofactor assay activity)
  
  CaseHPOFreeText: Haemarthrosis in teens, Delayed bleeding after tonsillectomy (DDAVP given prior to procedure), VWF:Ag (0·55–2 iu/ml) pre = 0·35, VWF:RCo (0·55–2 iu/ml) pre = 0·32, FVIII:C (0·55–2 iu/ml) pre = 0·12, FVIII:C/VWF:Ag ratio = 0·34, VWF:FVIII binding (>20%) = n/a, VWF:FVIII binding/VWF:Ag (>0·7) = n/a, Surgery to repair a syringomyelia defect with VWF concentrate and no bleeding complications
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: N/A
  
  ProteinExpression: N/A
  
  CasePreviousTesting: RFLP; confirmatory sequencing
  
  Gene: VWF
  
  Variant 1: NM_000552.4(VWF):c.2561G>A (p.Arg854Gln)
  
  ClinVar: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/
  
  gnomAD: MAF = 0.005692 (European Non-Finnish); https://gnomad.broadinstitute.org/variant/12-6143978-C-T
  
  Variant 2: N/A - stated to be a compound heterozygote for a 2N VWD and a presumed null mutation
  
  Individual CaseInfo InheritancePattern:AutosomalRecessive DiseaseEntity:VWD1 Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:296 inferred_gene_hgnc:12726 inferred_gene_source:RefSeq ClinGen VWF
Visit annotations in context

Tags

DiseaseEntity:VWD1

ClinGen VWF

Zygosity:CompoundHeterozygous

CaseInfo

inferred_gene_source:RefSeq

Mutation:Missense

InheritancePattern:AutosomalRecessive

ClinVarID:296

Individual

inferred_gene_hgnc:12726

Annotators

ClingenBaseline

URL

onlinelibrary-wiley-com.libproxy.lib.unc.edu/doi/full/10.1111/bjh.14028
www-nature-com.libproxy.lib.unc.edu www-nature-com.libproxy.lib.unc.edu

Newborn screening for Pompe disease in Japan: report and literature review of mutations in the GAA gene in Japanese and Asian patients

2
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  84
  
  Case#: 84, Gender N/A, 6 months old when diagnosed, Asian
  
  DiseaseAssertion: Pompe disease
  
  FamilyInfo: Both parents were tested for variants in GAA
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText:N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: The patient did not present any symptoms, diagnosed was made based on the predicted impact of the variant by PolyPhen-2
  
  CasePreviousTesting: The GAA gene was sequenced using NGS and resequenced for confirmation using Sanger.
  
  Dried Blood spot test found an GAA activity of 3.8 pmol/h/disk with a reference value of 6.5 pmol/h/disk
  
  enzyme activity in fibroblast was recorded to be 3.0 nmol/h/mg protein.
  
  Variants: Variant1: (Two mutated alleles with heterozygous mutations)
  
  Variant1.1: NM_000152.5(GAA):c.752C>T (p.Ser251Leu)
  
  ClinVar: 346310
  
  CAID: CA8815007
  
  gnomAD: Highest population MAF = 0.002234 (East Asian)
  
  Variant1.2: NM_000152.5(GAA):c.761C>T (p.Ser254Leu)
  
  ClinVar: 330447
  
  CAID: CA8815009
  
  gnomAD: Highest popu;ation MAF= 0.002235 (East Asians)
  
  Variant2: C.1244C>T
  
  ClinVar: N/A
  
  CAID: N/A
  
  gnomAD: N/A
  
  ParentalGenotype: The c.752C>T+c.761C>T and c.1244C>T of subject ID 84 were derived from mother and father, respectively
  
  PreviouslyPublished:N/A
  
  Individual CaseInfo DiseaseEntity:PompeDisease InheritancePattern:AutosomalRecessive Gene:GAA PreviousTesting:GAAmeasurement Zygosity:CompoundHeterozygous ClinVarID:346310 CAID:CA8815007 ClinVarID:330447 CAID:CA8815009 HGNC:4065 gene: GAA inferred_gene_hgnc:4065 inferred_gene_source:hgnc_tag GAA variant
2. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  93
  
  Case#: 93, gender N/A, 6months old when diagnosed, Asian
  
  DiseaseAssertion: Pompe disease
  
  FamilyInfo: Both parents were carriers of mutations in the GAA gene. The patient inherited the mutations.
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Symptoms were noted at the age of 2.7 months old
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: The patient showed no symptoms but LOPD was diagnosed based on the predicted impact of the variants by PolyPhen-2
  
  CasePreviousTesting: The GAA gene was sequenced using NGS and resequenced for confirmation using Sanger.
  
  Dried Blood spot test found an GAA activity of 0.25 pmol/h/disk with a reference value of 6.5 pmol/h/disk
  
  Variant1: NM_000152.5(GAA):c.317G>A (p.Arg106His)
  
  ClinVar: 286481
  
  CAID: CA8814849
  
  gnomAD: MAF=0.0001094 in East Asian
  
  Variant2: (COMBINATION OF MUTATIONS IN THIS ALLELE, DOUBT HERE)
  
  Variant2.1: NM_000152.5(GAA):c.752C>T (p.Ser251Leu)
  
  ClinVar: 346310
  
  CAID: CA8815007
  
  gnomAD: Highest population MAF = 0.002234 (East Asian)
  
  Variant2.2: NM_000152.5(GAA):c.761C>T (p.Ser254Leu)
  
  ClinVar: 330447
  
  CAID: CA8815009
  
  gnomAD: Highest population MAF= 0.002235 (East Asians)
  
  ParentalGenotype: Father is heterozygous for c.317G>A (p.Arg106His).
  
  Mother carries both mutations of c.[752C>T,761C>T].
  
  PreviouslyPublished:N/A
  
  Gene:GAA HGNC:4065 DiseaseEntity:PompeDisease PreviousTesting:GAAmeasurement Zygosity:CompoundHeterozygous ClinVarID:286481 CAID:CA8814849 ClinVarID:346310 CAID:CA8815007 Individual CaseInfo ClinVarID:330447 CAID:CA8815009 inferred_gene_hgnc:4065 inferred_gene_source:hgnc_tag GAA variant
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Tags

inferred_gene_hgnc:4065

inferred_gene_source:hgnc_tag

HGNC:4065

Gene:GAA

CAID:CA8815007

Zygosity:CompoundHeterozygous

CaseInfo

CAID:CA8815009

ClinVarID:286481

DiseaseEntity:PompeDisease

gene: GAA

InheritancePattern:AutosomalRecessive

PreviousTesting:GAAmeasurement

ClinVarID:330447

ClinVarID:346310

Individual

GAA variant

CAID:CA8814849

Annotators

ClingenBaseline

URL

www-nature-com.libproxy.lib.unc.edu/articles/s10038-019-0603-7
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Antagonistic Roles of Human Platelet Integrin αIIbβ3 and Chemokines in Regulating Neutrophil Activation and Fate on Arterial Thrombi Under Flow

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  patient 2
  
  Case#: patient 2
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  **FamilyInfo: **
  
  ParentalGenotype: If noted by authors, annotate with the carrier status of each parent in regards to the variant(s) identified in the proband.
  
  CasePresentingHPOs:
  
  PlateletAggregation: absent platelet integrin αIIbβ3. Monolayer of spread platelets essentially devoid of fibrinogen binding but with high CD62P expression and phosphatidylserine exposure (Figure S1). Figure 5.
  
  CaseHPOFreeText:
  
  CaseNotHPOs:
  
  **CaseNotHPOFreeText: **
  
  ProteinExpression:
  
  CasePreviousTesting:
  
  **PreviouslyPublished: **
  
  Gene: ITGA2B
  
  **HGVS: **
  
  **ClinVar: **
  
  CAID:
  
  **gnomAD: **
  
  Gene: ITGA2B
  
  **HGVS: ** NM_000419.5:c.2051T>G
  
  **ClinVar: ** 1330350
  
  CAID: CA399799849
  
  **gnomAD: **
  
  UnregisteredVariant Zygosity:CompoundHeterozygous Mutation:Missense DiseaseEntity:GlanzmannThrombasthenia CAid:CA399799849 ClinVarID:1330350 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

inferred_gene_hgnc:6138

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

ClinVarID:1330350

inferred_gene_source:CAID

UnregisteredVariant

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CAid:CA399799849

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC10443630/
europepmc.org europepmc.org

In silico analysis of structural modifications in and around the integrin αIIb genu caused by ITGA2B variants in human platelets with emphasis on Glanzmann thrombasthenia

3
1. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplemental Table S1:
 
 Cases26-33: Males and Females from France, Spain and Italy and ages are not specified
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: Mild to severe bleeding for probands
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: 8-20% αIIbβ3 expression
 
 PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
 
 CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.2113T>C (p.Cys705Arg)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8602816
 
 gnomAD: MAF in the European non finnish population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G
 
 PreviouslyPublished: PMID: 9920835, 12083483, 12424194, 25728920, 20020534
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous Zygosity:Homozygous PreviousTesting:Full CAiD:CA8602816 ProteinExpression:Reported PlateletAggregation:MinimalInformation PreviouslyPublished SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 22 Oct 2026
 
 in Baseline Annotations
 
 Supplemental Table S1:
 
 Case3: Male, USA, age not specified
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: N/A
 
 CaseHPOFreeText: Severe life threatening bleeding
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: >5% αIIbβ3 expression
 
 PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
 
 CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1553T>A (p.Ile518Asn) and NM_000419.3:c.1946+3G>T
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA8603038 and CA626121071
 
 gnomAD: MAF in the European (non-Finnish) population is 0.000008790 https://gnomad.broadinstitute.org/variant/17-42457661-A-T and MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42456008-C-A
 
 PreviouslyPublished: PMID: 25728920
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Intronic Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full CAiD:CA8603038 CAiD:CA626121071 ProteinExpression:Reported PlateletAggregation:MinimalInformation PreviouslyPublished SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
3. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 Supplemental Table S1:
 
 Case12: Male, Italy, age not specified
 
 DiseaseAssertion: Glanzmann thrombasthenia
 
 FamilyInfo: N/A
 
 ParentalGenotype: N/A
 
 CasePresentingHPOs: Moderate bleeding
 
 CaseHPOFreeText: N/A
 
 CaseNotHPOs: N/A
 
 CaseNotHPOsFreeText: N/A
 
 ProteinExpression: <5% αIIbβ3 expression
 
 PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
 
 CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
 
 Gene: ITGA2B
 
 Variant: NM_000419.3:c.1742C>A (p.Ala581Asp)
 
 LegacyVariant: N/A
 
 ClinVar: N/A
 
 CAiD: CA399802112
 
 gnomAD: N/A
 
 PreviouslyPublished: PMID: 12083483
 
 CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399802112 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:MinimalInformation PreviouslyPublished SupplementalData inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

PreviousTesting:Full

inferred_gene_source:CAID

Mutation:Intronic

ClinGen ITGA2B/ITGB3

CAiD:CA8603038

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

CAiD:CA399802112

CAiD:CA8602816

PlateletAggregation:MinimalInformation

Individual

CAiD:CA626121071

ProteinExpression:Reported

SupplementalData

Zygosity:Homozygous

PreviouslyPublished

Annotators

ClingenBaseline

URL

europepmc.org/article/med/29385657
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

A novel variant Glanzmann thrombasthenia due to co-inheritance of a loss- and a gain-of-function mutation of ITGB3: evidence of a dominant effect of gain-of-function mutations

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  The proband was a 27-year old Danish woman
  
  Case1: Female, 27 years old, Danish
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Information on father, mother, brother and sister. (See Figure 1 for pedigree)
  
  ParentalGenotype: Pedigree from Figure 1 shows Father to have (p.Asn331Ser) and mother has (p.Arg786Trp) variant.
  
  CasePresentingHPOs: HP:0000978, HP:0001934, HP:0006298
  
  (Bruising, prolonged bleeding after minor trauma, prolonged bleeding after dental extraction)
  
  CaseHPOFreeText: Lifelong bleeding history
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: αIIbβ3 expression and activation and αvβ3 expression were assessed by flow cytometry (See Figure 1 and 2 for results)
  
  PlateletAggregation: Platelet aggregation was impaired in response to all stimuli except ristocetin, with low-normal response to collagen
  
  CasePreviousTesting: To identify DNA variants, all exons of ITGA2B and ITGB3 were analyzed by Sanger sequencing
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.2356C>T (p.Arg786Trp) an NM_000212.2:c.992A>G (p.Asn331Ser)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA400034866 (p.Arg786Trp) and CA400025729 (p.Asn331Ser)
  
  gnomAD: MAF for (p.Arg786Trp) in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-45387559-C-T
  
  Individual CaseInfo Gene:ITGB3 DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:NoZygosityAssertion InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous CAiD:CA400034866 CAiD:CA400025729 PreviousTesting:Full FamilyInfo ParentalTesting:FullPhase ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

PreviousTesting:Full

Zygosity:NoZygosityAssertion

inferred_gene_source:CAID

FamilyInfo

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

CAiD:CA400034866

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

Individual

inferred_gene_hgnc:6156

ProteinExpression:Reported

CAiD:CA400025729

PlateletAggregation:Reported

Gene:ITGB3

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC6058799/
www.tandfonline.com www.tandfonline.com

CPLA_A_477674_P 498..500

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  male patient
  
  Case1: Male, French, age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Son was heterozygous carriers of the p.Leu196Pro mutation (Sister died from nasal bleeding when she was a child)
  
  ParentalGenotype: Mother is heterozygous for p.Leu196Pro mutation (Father not alive)
  
  CasePresentingHPOs: HP:0000421 (Epistaxis)
  
  CaseHPOFreeText: Lifelong history of mucocutaneous bleeding
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Expression showed 8% of normal platelet content for αIIbβ3
  
  PlateletAggregation: Absent aggregation to physiologic agonists
  
  CasePreviousTesting: Screened exons and splice sites of ITGB3 and ITGA2B genes of patient by single-strand conformation polymorphism analysis of PCR products.
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.665T>C (Leu222Pro) and NM_000212.2:c.1871G>A (p.Cys624Tyr)
  
  LegacyVariant: p.Leu196Pro and p.Cys598Tyr
  
  ClinVar: N/A
  
  CAiD: CA291224887 and CA400032726
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Full FamilyInfo:Minimal ParentalTesting:PartialPhase ProteinExpression:Reported PlateletAggregation:Reported CAiD:CA291224887 CAiD:CA400032726 inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

PreviousTesting:Full

FamilyInfo:Minimal

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

CAiD:CA400032726

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

ParentalTesting:PartialPhase

InheritancePattern:AutosomalRecessive

Individual

CAiD:CA291224887

inferred_gene_hgnc:6156

ProteinExpression:Reported

PlateletAggregation:Reported

Gene:ITGB3

Annotators

ClingenBaseline

URL

tandfonline.com/doi/pdf/10.3109/09537101003771528
Local file Local file

Novel mutations in Thai patients with glanzmann thrombasthenia

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  3
  
  Case3: Gender or age not specified, Thai ethnicity
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Parental information available in Table 2
  
  ParentalGenotype: Father: p.Arg782Ter/WT and Mother: Unavailable
  
  Note: No parental consanguinity
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: The article does not mention specific bleeding phenotypes for each of the 4 probands in the article, rather, there is a general statement that says: "The common presentations included recurrent epistaxis, bleeding in oral cavity, and easy-bruising spontaneously or after trauma"
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinEpression: General statement from the article that states that flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression for all probands.
  
  PlateletAggregation: The platelet aggregation test was typically defective with all physiological agonists except ristocetin, for all patients.
  
  CasePreviousTesting: Whole exome sequencing was performed on the 30 exons of ITGA2B and 15 exons in ITGB3. PCR and direct sequencing were then performed in the DNA samples of the patients and their available parents to verify the presence of the identified mutations.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2344C>T (p.Arg782Ter) and NM_000419.3:c.2915dup (p.Leu973Alafs*63)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399796586 (p.Arg782Ter) and CA8602531 (p.Leu973Alafs*63)
  
  gnomAD: MAF for (p.Leu973Alafs*63) in East Asian population 0.0001088 http://gnomad.broadinstitute.org/variant/17-42452054-C-CG
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion Mutation:Frameshift Mutation:Nonsense Zygosity:CompoundHeterozygous CAiD:CA399796586 CAiD:CA8602531 PreviousTesting:Full ParentalTesting:PartialPhase ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

CAiD:CA399796586

PreviousTesting:Full

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

ParentalTesting:PartialPhase

Individual

CAiD:CA8602531

ProteinExpression:Reported

Mutation:Frameshift

PlateletAggregation:Reported

Annotators

ClingenBaseline
watermark.silverchair.com watermark.silverchair.com

3212.pdf

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  Recently, we reported the case of an 8-year-old boy with a variant form of GT
  
  Case1: Male, 8 years old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: Sister had no bleeding tendency (all the information given in the previously published article cited in this annotation)
  
  ParentalGenotype: Parental mutations shown in Fig. 3 A and B
  
  CasePresentingHPOs: HP:0000421
  
  (Epistaxis)
  
  CaseHPOFreeText: Tonsilar bleeding
  
  CaseNotHPOs: HP:0000979
  
  (Purpura)
  
  CaseNotHPOFreeText: N/A
  
  ProteinExpression: Western blotting indicated that the proband's platelets contained no normal GPIIb, but showed a trace amount of an abnormal GPIIb (-6% with respect to the GPIIb level in a normal individual).
  
  PlateletAggregation: Decreased aggregation in response to ADP, collagen and epinephrine but a normal ristocetin-induced aggregation (this information was obtained from the previously published article cited at in this annotation)
  
  CasePreviousTesting: Genomic DNA fragments containing exons of the GPIIb gene were amplified by PCR
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.2602-3C>G
  
  LegacyVariant: N/A
  
  ClinVar: 2892 and 2893
  
  CAiD: CA115834 and CA10575472
  
  gnomAD: MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A and MAF in the East Asian population is 0.00006523 https://gnomad.broadinstitute.org/variant/17-42453087-G-C
  
  PreviouslyPublished: PMID: 1891767
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense Mutation:Intronic Zygosity:CompoundHeterozygous ClinVarID:2892 ClinVarID:2893 CAiD:CA115834 CAiD:CA10575472 PreviousTesting:Partial FamilyInfo:Minimal ProteinExpression:Reported PlateletAggregation:Reported PreviouslyPublished ParentalTesting:FullPhase inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

ClinVarID:2893

ClinVarID:2892

FamilyInfo:Minimal

inferred_gene_source:CAID

Mutation:Intronic

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

PreviousTesting:Partial

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

CAiD:CA115834

DiseaseEntity:GlanzmannThrombasthenia

CAiD:CA10575472

ParentalTesting:FullPhase

Individual

ProteinExpression:Reported

PlateletAggregation:Reported

PreviouslyPublished

Annotators

ClingenBaseline

URL

watermark.silverchair.com/3212.pdf
Local file Local file

Jackson_et_al-2017-European_Journal_of_Biochemistry.pdf

1
1. ClingenBaseline 22 Oct 2026
  
  in Baseline Annotations
  
  A Glanzmann patient, LeM
  
  Case2: Patient LeM
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs:
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Platelets lack surface αIIbβ3 expression
  
  PlateletAggregation: N/A
  
  CasePreviousTesting: N/A
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1366_1371del V(425)D(426)del and other other variant is stated as "Unknown" in the GT database. See GT database if questions arise, this is where I found the variants
  
  LegacyVariant: N/A
  
  ClinVar: 2898
  
  CAiD: CA8603160
  
  gnomAD: MAF in the European (non-Finnish) population is 0.000008791 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000419.3%3Ac.1366_1371del
  
  CaseInfo Individual Gene:ITGA2B Mutation:Large Zygosity:CompoundHeterozygous DiseaseEntity:GlanzmannThrombasthenia InheritancePattern:NoInheritanceAssertion ProteinExpression:MinimalInformation PlateletAggregation:NotReported ClinVarID:2898 CAiD:CA8603160 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

inferred_gene_hgnc:6138

DiseaseEntity:GlanzmannThrombasthenia

InheritancePattern:NoInheritanceAssertion

ProteinExpression:MinimalInformation

Individual

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

PlateletAggregation:NotReported

Zygosity:CompoundHeterozygous

CAiD:CA8603160

CaseInfo

Gene:ITGA2B

Mutation:Large

ClinVarID:2898

Annotators

ClingenBaseline
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Induced Pluripotent Stem Cells to Understand Mucopolysaccharidosis. I: Demonstration of a Migration Defect in Neural Precursors

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  2-year-old male MPS1-H child
  
  Case#: Male, 2-year old
  
  DiseaseAssertion: MPS1-H
  
  FamilyInfo: Not provided
  
  CasePresentingHPOs: Not provided
  
  CaseHPOFreeText: NA
  
  CaseNotHPOs: Not provided
  
  CaseNotHPOFreeText: NA
  
  CaseEnzymeAssay: MPS1-H fibroblasts exhibited no activity of IDUAα (0.01 ± 0.02 nmol/mg/min); iPSC clones were devoid of IDUAα activity
  
  CaseUrineGAGs: Not provided
  
  CaseERT: Don't know
  
  CaseBMT: Don't know
  
  Variant1: NM_000203.5(IDUA):c.1073_1093del (p.His358_Thr364del)
  
  Variant1ClinVarID:557260
  
  Variant1CAID:
  
  Variant2: NM_000203.4(IDUA):c.1205 G>A (p.Trp402Ter)
  
  Variant2ClinVarID:11908
  
  Variant2CAID:
  
  ParentalGenotype: Not provided
  
  PreviouslyPublished: Authors reference [30]: PMID: 31678774 DOI: 10.1016/j.scr.2019.101604
  
  Gene:IDUA HGNC:5391 Mutation:Inframe Mutation:Nonsense PMC:PMC7761689 InheritancePattern:AutosomalRecessive DiseaseEntity:MPS1 ClinVarID:557260 ClinVarID:11908 Zygosity:CompoundHeterozygous inferred_gene_hgnc:5391 inferred_gene_source:hgnc_tag IDUA variant annotation
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Tags

ClinVarID:11908

InheritancePattern:AutosomalRecessive

Gene:IDUA

inferred_gene_source:hgnc_tag

Mutation:Inframe

DiseaseEntity:MPS1

inferred_gene_hgnc:5391

Mutation:Nonsense

PMC:PMC7761689

IDUA variant annotation

Zygosity:CompoundHeterozygous

ClinVarID:557260

HGNC:5391

Annotators

ClingenBaseline

URL

pmc.ncbi.nlm.nih.gov/articles/PMC7761689/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Type 2B von Willebrand disease with or without large multimers: A distinction of the two sides of the disorder is long overdue

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  3
  
  Case: Patient 3 (Family B), male, 55yo
  
  DiseaseAssertion: VWD2B
  
  FamilyInfo: NA
  
  ParentalGenotype(s): NA
  
  CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147
  
  (impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)
  
  CaseHPOFreeText: blood group O, Platelet count x103/μl = 204, PFA 100 sec = >300, SPA % = 0, MADR mg/mL = 0.45, VWF:Ag U/dL = 23.4, VWF:CB U/dL = 21.1, VWF:CB ratio = 0.9, VWF:RCo U/dL = 17.2, VWF:RCo ratio = 0.74, Platelet VWF U/dL = 42.6, FVIII U/dL = 60.5, BAT F/M = 20
  
  CaseNOTHPOs:
  
  CaseNOTHPOFreeText:
  
  CasePreviousTesting: NA
  
  GenotypingMethod: Sequencing of exon 28 of VWF
  
  PreviouslyPublished: NA
  
  Gene: VWF
  
  Variant 1: c.3797C>T (p.Pro1266Leu)
  
  HGVS: NM_000552.4(VWF):c.3797C>T (p.Pro1266Leu)
  
  ClinVarID: 314; https://www.ncbi.nlm.nih.gov/clinvar/variation/314/
  
  CAID: NA
  
  gnomAD: MAF = 0.003667 (92/25086 alleles; 1 homozygote) in the European (Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128787-G-A?dataset=gnomad_r2_1
  
  Variant 2: c.7085G>T (p.Cys2362Phe)
  
  HGVS: NM_000552.4(VWF):c.7085G>T (p.Cys2362Phe)
  
  ClinVarID: 315; https://www.ncbi.nlm.nih.gov/clinvar/variation/315/
  
  CAID: NA
  
  gnomAD: absent
  
  Individual CaseInfo Gene:VWF DiseaseEntity:VWD2B InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous Mutation:Missense ClinVarID:314 ClinVarID:315 inferred_gene_hgnc:12726 inferred_gene_source:Gene_Name ClinGen VWF
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Tags

Mutation:Missense

InheritancePattern:AutosomalRecessive

inferred_gene_source:Gene_Name

DiseaseEntity:VWD2B

ClinVarID:315

Individual

inferred_gene_hgnc:12726

ClinGen VWF

ClinVarID:314

Zygosity:CompoundHeterozygous

CaseInfo

Gene:VWF

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC5480883/
ashpublications-org.libproxy.lib.unc.edu ashpublications-org.libproxy.lib.unc.edu

Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor

1
1. ClingenBaseline 21 Oct 2026
 
 in Baseline Annotations
 
 In family 1, the proposita (1A)
 
 Case#: 1A
 
 DiseaseAssertion:
 
 FamilyInfo: Family 1. Her 2 offspring, 1B (son) and 1C (daughter), reported minor bleeding symptoms that had not required treatment. 1B was found to be heterozygous for Trp1745Cys only and 1C was heterozygous for Arg760His only, confirming that these mutations are in trans in 1A.
 
 CaseHPOFreeText4: was an elderly woman with lifelong bleeding episodes, including epistaxis, ecchymosis, menorrhagia, and prolonged bleeding after dental extractions, requiring multiple medical interventions. The coexistence of both mutations appears to produce a more significant bleeding disorder as the bleeding score in 1A (8) was higher than that in either of her children (4 and 2). The position of Trp1745 in the A3 domain is shown in Figure 2. Both persons with this mutation (1A and 1B) had markedly reduced ratios of VWF collagen-binding activity to VWF antigen (CB:Ag) with type III collagen (0.1 and 0.3, respectively) and type I collagen (0.2 and 0.3, respectively). The ratio of VWF:RCo to VWF:Ag (RCo:Ag) was near unity in both persons, and VWF multimer analysis (Figure 1B) and RIPA were normal. Closure times in the PFA-100 were mildly prolonged with the ADP cartridge (1A = 173 seconds, 1B = 189 seconds, NR < 112 seconds). With the epinephrine cartridge, the closure time was prolonged in 1A only (1A = 271 seconds, 1B = 90 seconds, NR < 179 seconds).
 
 CasePreviousTesting: Fifty-one primer sets were used to amplify the essential regions of VWF (52 exons, flanking intronic regions, 5′ promoter region, and the 3′ untranslated region).
 
 Gene: VWF
 
 Variant: 1A demonstrated compound heterozygosity for 2 mutations in the VWF gene. The first is a novel mutation in exon 30:c.5235 G → T resulting in Trp1745Cys and the second is c.2279 G → A resulting in Arg760His.
 
 HGVS: NM_000552.5(VWF):c.5235G>T (p.Trp1745Cys), NM_000552.5(VWF):c.2279G>A (p.Arg760His)
 
 ClinVar: 100421, 31011
 
 CAID: CA228706, CA228316
 
 gnomAD: 8.474e-7 in the european non finnish pop, 0.00002669 in the African American population
 
 InheritancePattern:AutosomalRecessive DiseaseEntity:VWD2 Mutation:Missense Zygosity:CompoundHeterozygous ClinVar: 100421 ClinVar: 31011 inferred_gene_hgnc:12726 inferred_gene_source:CAID ClinGen VWF
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Tags

Mutation:Missense

ClinVar: 31011

InheritancePattern:AutosomalRecessive

inferred_gene_source:CAID

inferred_gene_hgnc:12726

ClinGen VWF

Zygosity:CompoundHeterozygous

ClinVar: 100421

DiseaseEntity:VWD2

Annotators

ClingenBaseline

URL

ashpublications-org.libproxy.lib.unc.edu/blood/article/114/16/3489/26287/Characterization-of-W1745C-and-S1783A-2-novel
Local file Local file

A Val193Met mutation in GPIIIa results in a GPIIb/IIIa receptor with a constitutively high affinity for a small ligand

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  GTa, a 37-year-old female IrishCaucasian
  
  Case1: (GTa) Female, 27 years old, Irish Caucasian
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: No family history of bleeding
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0000978
  
  (Bruising)
  
  CaseHPOFreeText: Excessive bleeding after a normal delivery
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Reduced expression of GPIIb/IIIa
  
  PlateletAggregation: Platelet aggregation to ADP, thrombin receptor activating peptide, thrombin and U46619 was less than 10% and ristocetin induced agglutination was normal
  
  CasePreviousTesting: Total RNA isolated from the proband's platelets was used as a template for RT PCR. Seven primer pairs were used to amplify overlapping regions of the entire GPIIIa coding sequence using cDNA template
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.655G>A (p.Val219Met)
  
  LegacyVariant: (p.Val193Met)
  
  ClinVar: N/A
  
  CAiD: CA8623016
  
  gnomAD: MAF in the South Asian population is 0.00003266 http://gnomad.broadinstitute.org/variant/17-45363666-G-A
  
  CaseInfo Individual Gene:ITGB3 InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Partial ProteinExpression:Reported PlateletAggregation:Reported FamilyInfo:Minimal inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

DiseaseEntity:GlanzmannThrombasthenia

InheritancePattern:NoInheritanceAssertion

Mutation:Missense

FamilyInfo:Minimal

Individual

PlateletAggregation:Reported

inferred_gene_hgnc:6156

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

PreviousTesting:Partial

ProteinExpression:Reported

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGB3

Annotators

ClingenBaseline
clinchem.aaccjnls.org clinchem.aaccjnls.org

746.full.pdf

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  A 3-year-old girl
  
  Case1: Female, 3 year old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: An analysis of family members indicated that the Gln517Stop and Arg553Stop mutations were located on different alleles and inherited from the patient’s mother and father, respectively
  
  CasePresentingHPOs: HP:0004406, HP:0002248, HP:0000978, HP:0000225
  
  (Recurrent epistaxis, hematemesis, easy bruising, gingival bleeding)
  
  CaseHPOFreeText: Petechial hemorrhages
  
  CaseNotHPOs: HP:0001945, HP:0002014, HP:0005261
  
  Fever, diarreah, hemarthrosis
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: A flow cytometry evaluation revealed marked reduction in glycoprotein IIb/IIIa (See Table 1 for Patient's Lab results)
  
  PlateletAggregation: Patients platelets did not aggregate in response to ADP, epinephrine, arachidonic acid, or collagen but platelets had normal ristocetin induced aggregation
  
  CasePreviousTesting: Molecular genetic analysis of ITGA2B was performed which revealed mutations
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1642C>T (p.Gln548Ter) and NM_000419.3:c.1750C>T (Arg584Ter)
  
  LegacyVariant: Gln517Ter and Arg553Ter
  
  ClinVar: 2892
  
  CAiD: CA399802364 and CA115834
  
  gnomAD: MAF in the East Asian population is 0.0002176
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous DiseaseEntity:GlanzmannThrombasthenia Mutation:Nonsense CAiD:CA915940226 CAiD:CA115834 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Visit annotations in context

Tags

CAiD:CA115834

DiseaseEntity:GlanzmannThrombasthenia

InheritancePattern:AutosomalRecessive

PreviousTesting:Full

Individual

PlateletAggregation:Reported

inferred_gene_hgnc:6156

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

ProteinExpression:Reported

Zygosity:CompoundHeterozygous

CaseInfo

CAiD:CA915940226

Gene:ITGA2B

Annotators

ClingenBaseline

URL

clinchem.aaccjnls.org/content/clinchem/59/5/746.full.pdf
www.thieme-connect.com www.thieme-connect.com

Characterisation of patients with Glanzmann thrombasthenia and identification of 17 novel mutations

2
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  GT12
  
  Case12: GT-12, Caucasian, gender or age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: Mother: c.2326_2331dupGAGGCC and Father: deceased
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1
  
  PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned
  
  CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.957T>A and NM_000419.3:c.2326_2331dupGAGGCC
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA399804780 and CA915940324
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:Frameshift Mutation:Missense Zygosity:CompoundHeterozygous CAiD:CA399804780 CAiD:CA915940324 PreviousTesting:Full ParentalTesting:FullPhase ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
2. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  GT5
  
  Case5: GT-5, Caucasian, gender or age not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1
  
  PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned
  
  CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.408G>C and NM_000419.3:c.1787T>C
  
  LegacyVariant: N/A
  
  ClinVar: 2900
  
  CAiD: CA500624244 and CA115846
  
  gnomAD: MAF in the European (non-Finnish) population 0.00006484 http://gnomad.broadinstitute.org/variant/17-42463192-C-G and MAF in European (non-Finnish) population is 0.0001325 http://gnomad.broadinstitute.org/variant/17-42457148-A-G
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:2900 CAiD:CA500624244 CAiD:CA115846 PreviousTesting:Full ProteinExpression:MinimalInformation PlateletAggregation:MinimalInformation inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

inferred_gene_hgnc:6138

ClinVarID:2900

InheritancePattern:NoInheritanceAssertion

CAiD:CA500624244

PreviousTesting:Full

ProteinExpression:MinimalInformation

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CAiD:CA115846

CaseInfo

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

PlateletAggregation:MinimalInformation

Individual

CAiD:CA399804780

Mutation:Frameshift

CAiD:CA915940324

Annotators

ClingenBaseline

URL

thieme-connect.com/products/ejournals/pdf/10.1160/TH14-05-0479.pdf
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Management challenge of a rare concomitant platelet glycoprotein IV/CD36 and IIb/IIIa deficiencies: Case illustration

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  A 62‐year‐old Egyptian male
  
  Case#: Male, 62, Egyptian
  
  DiseaseAssertion: GT with concurrent platelet CD36 deficiency (~1 in 100 million) and anti‐CD36 antibodies
  
  CasePresentingHPOs: HP:0000421,Epistaxis. HP:0000978, Bruising susceptibility. HP:0000225, Gingival bleeding. HP:0001903, Anemia. HP:0001934, Persistent bleeding after trauma. HP:0001058, Poor wound healing. HP:0002573, Hematochezia. HP:0005261, Joint hemorrhage.
  
  PlateletAggregation: See Table 1. Normal platelet count. Normal platelet size, modestly elevated mean platelet volume. Normal response to ristocetin.
  
  ProteinExpression: Flow cytometry. GPIb/IX Expression 108% (range: 65-124%); GPIIb/IIIa expression 0% (range:65-124%).
  
  Gene: ITGA2B
  
  Variant: c.2148dup, p.Leu717Alafs3X
  
  HGVS: NM_000419.5:c.2148dup
  
  ClinVar: 627273
  
  CAID: CA915940304
  
  gnomAD: Absent
  
  Variant: c.1234G>A, p.Gly412Arg
  
  HGVS: NM_000419.5:c.1234G>A
  
  ClinVar: 381748
  
  CAID: CA8603182
  
  gnomAD: 0.00003236, https://gnomad.broadinstitute.org/variant/chr17-44381038-C-T?dataset=gnomad_r4
  
  InheritancePattern:AutosomalRecessive DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:627273 CAid:CA915940304 ClinVarID:381748 CAid:CA8603182 MultipleGeneVariants PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

MultipleGeneVariants

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

inferred_gene_hgnc:6138

InheritancePattern:AutosomalRecessive

PreviousTesting:Full

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

ClinVarID:381748

CAid:CA915940304

ClinVarID:627273

ProteinExpression:Reported

Zygosity:CompoundHeterozygous

PlateletAggregation:Reported

CAid:CA8603182

Annotators

ClingenBaseline

URL

pmc.ncbi.nlm.nih.gov/articles/PMC12005580/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Demonstration of novel gain-of-function mutations of αIIbβ3: association with macrothrombocytopenia and glanzmann thrombasthenia-like phenotype

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Case 1
  
  Case1: Female, 9 years old, Japanese
  
  DiseaseAssertion: Macrothrombocytopenia
  
  FamilyInfo: Information given in Table 1 and Fig 2
  
  ParentalGenotype: Mother: ITGA2B (p.Arg422Ter heterozygous) and Father: ITGA2B (p.Gly991Cys heterozygous) See Table 1 for this information
  
  Sequencing of parental DNA indicated parental mutations. CasePresentingHPOs: HP:0000979, HP:0000421, HP:0000978
  
  (Purpura, epistaxis, bruising)
  
  CaseHPOFreeText: Hemorrhage after dental
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometric analysis showed that surface αIIbβ3 expression in platelets (was markedly impaired 3-11%)
  
  PlateletAggregation: N/A
  
  CasePreviousTesting: Sequence analysis of entire coding regions of exons and exon-intron boundaries of ITGA2B and ITGB3 gene of the patient revealed two novel mutations in ITGA2B.
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.3064G>T (p.Gly1022Cys) and NM_000419.3:c.1357C>T (p.Arg453Ter)
  
  LegacyVariant: (p.Gly991Cys legacy nomenclature for p.Gly1022Cys) and (p.Arg422Ter legacy nomenclature for p.Arg453Ter)
  
  ClinVar: 631773
  
  CAiD: CA399787943 and CA399803529
  
  gnomAD: N/A
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:AutosomalRecessive DiseaseEntity:Macrothrombocytopenia Mutation:Nonsense Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:631773 CAiD:CA399787943 CAiD:CA399803529 PreviousTesting:Full FamilyInfo:Minimal ParentalTesting:FullPhase ProteinExpression:Reported PlateletAggregation:NotReported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

inferred_gene_hgnc:6138

ClinVarID:631773

CAiD:CA399787943

CAiD:CA399803529

PreviousTesting:Full

FamilyInfo:Minimal

inferred_gene_source:CAID

DiseaseEntity:Macrothrombocytopenia

ClinGen ITGA2B/ITGB3

Mutation:Nonsense

PlateletAggregation:NotReported

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

Mutation:Missense

InheritancePattern:AutosomalRecessive

ParentalTesting:FullPhase

Individual

ProteinExpression:Reported

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC3865572/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Molecular genetic diagnosis of Glanzmann syndrome in Iranian population; reporting novel and recurrent mutations

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  5
  
  Case5: No assertion made on age, gender or ethnicity
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: The identified variants were heterozygote in parents.
  
  CasePresentingHPOs: N/A
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: N/A
  
  CasePreviousTesting: Genetic study of patient was conducted using direct sequencing of entire coding and exon-intron boundaries of the ITGA2B and ITGB3 genes.
  
  Gene: ITGB3
  
  Variant: NM_000212.2:c.538G>A (p.Gly180Arg) and NM_000212.2:c.155G>T (p.Cys52Phe)
  
  LegacyVariant: N/A
  
  ClinVar: N/A
  
  CAiD: CA8622972 (p.Gly180Arg) CA8622859 (p.Cys52Phe)
  
  gnomAD: "Other" population (p.Gly180Arg) MAF is 0.0001630 https://gnomad.broadinstitute.org/variant/17-45361985-G-A and South Asian population p.Cys52Phe) MAF is 0.00003266.
  
  Individual CaseInfo Gene:ITGB3 DiseaseEntity:GlanzmannThrombasthenia InheritancePattern:AutosomalRecessive Mutation:Missense CAiD:CA8622972 CAiD:CA8622859 Zygosity:CompoundHeterozygous ProteinExpression:NotReported inferred_gene_hgnc:6156 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

CAiD:CA8622859

InheritancePattern:AutosomalRecessive

CAiD:CA8622972

Individual

inferred_gene_source:CAID

inferred_gene_hgnc:6156

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

ProteinExpression:NotReported

Gene:ITGB3

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pmc/articles/PMC6487065/
Local file Local file

Description of 10 new mutations in platelet glycoprotein IIb (alphaIIb) and glycoprotein IIIa (beta3) genes alpha

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  FO
  
  Case7: Patient FO
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs:
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: N/A
  
  PlateletAggregation: N/A
  
  CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2153dup and NM_000419.3:c.1234G>A (p.Gly412Arg)
  
  LegacyVariant: (p.Gly381Arg)
  
  ClinVar: 381748
  
  CAiD: CA913189170 and CA8603182
  
  gnomAD MAF in the Latino population is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Insertion PreviousTesting:Full CAiD:CA913189170 ProteinExpression:NotReported PlateletAggregation:NotReported CAiD:CA8603182 ClinVarID:381748 Zygosity:CompoundHeterozygous inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
Tags

inferred_gene_hgnc:6138

Mutation:Insertion

InheritancePattern:NoInheritanceAssertion

PreviousTesting:Full

inferred_gene_source:CAID

CAiD:CA913189170

PlateletAggregation:NotReported

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CAiD:CA8603182

CaseInfo

Gene:ITGA2B

ProteinExpression:NotReported

DiseaseEntity:GlanzmannThrombasthenia

Individual

ClinVarID:381748

Annotators

ClingenBaseline
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Spontaneous hemarthrosis in combined Glanzmann thrombasthenia and type 2N von Willebrand disease. - PubMed - NCBI

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  Case1: Female, 48 years old, ethnicity not specified
  
  DiseaseAssertion: Glanzmann thrombasthenia
  
  FamilyInfo: N/A
  
  ParentalGenotype: N/A
  
  CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000978, HP:0000132, HP:0006298, HP:0005261
  
  (Epistaxis, gingival bleeding, easy bruising, menorrhagia, bleeding after tooth extraction, hemarthrosis
  
  CaseHPOFreeText: Hemorrhage after surgery
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Platelet surface glycoprotein analysis by flow cytometry revealed a severe αIIbβ3 deficiency (Table 3 shows specific values)
  
  PlateletAggregation: There was a failure of ADP, collagen and adrenalin to induce platelet aggregation, but ristocetin-induced platelet aggregation (RIPA) was normal
  
  CasePreviousTesting: Integrin alphaIIb subunit gene (ITGA2B) sequencing showed that this proband was a compound heterozygote
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.1214T>C (p.Ile405Thr) and NM_000419.3:c.1234G>A (p.Gly412Arg)
  
  LegacyVariant: (p.Ile374Thr) (p.Gly381Arg)
  
  ClinVar: 381748
  
  CAiD: CA290950815 (p.Ile403Thr) and CA8603182 (p.Gly412Arg)
  
  gnomAD: MAF in Latino population 0.0001453 http://gnomad.broadinstitute.org/variant/17-42458406-C-T
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous PreviousTesting:Partial ClinVarID:381748 CAiD:CA290950815 CAiD:CA8603182 inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

inferred_gene_hgnc:6138

DiseaseEntity:GlanzmannThrombasthenia

InheritancePattern:NoInheritanceAssertion

Mutation:Missense

Individual

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

ClinVarID:381748

PreviousTesting:Partial

CAiD:CA290950815

CAiD:CA8603182

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

Annotators

ClingenBaseline

URL

ncbi.nlm.nih.gov/pubmed/24418945
link.springer.com link.springer.com

Successful management of perioperative hemostasis in a patient with Glanzmann thrombasthenia who underwent a right total mastectomy

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  A 56-year-old Japanese female
  
  Case1: Female, 56 years old, Japanese
  
  DiseaseAssertion: Glanzmann thrombasthenia (Diagnosed at 21 years of age)
  
  FamilyInfo:
  
  ParentalGenotype:
  
  CasePresentingHPOs: HP:0004406, HP:0000225
  
  (Recurrent epistaxis, gingival bleeding)
  
  CaseHPOFreeText: N/A
  
  CaseNotHPOs: N/A
  
  CaseNotHPOsFreeText: N/A
  
  ProteinExpression: Flow cytometry demonstrated significantly decreased expression of CD41 and CD61 to less than 20% of normal levels (See Figure 2)
  
  PlateletAggregation: An in vitro assay revealed no platlet aggregation in response to agonists except ristocetin.
  
  CasePreviousTesting: DNA sequencing analysis revealed compound heterozygous mutations confirming a diagnosis of Glanzmann thrombasthenia
  
  Gene: ITGA2B
  
  Variant: NM_000419.3:c.2602-3C>G and NM_000419.3:c.641T>C (p.Leu214Pro)
  
  LegacyVariant: N/A
  
  ClinVar: 2893 and 2901
  
  CAiD: CA10575472 and CA115848
  
  gnomAD: MAF in East Asian population 0.00006523 http://gnomad.broadinstitute.org/variant/17-42453087-G-C
  
  CaseInfo Individual Gene:ITGA2B InheritancePattern:NoInheritanceAssertion DiseaseEntity:GlanzmannThrombasthenia Mutation:Missense Zygosity:CompoundHeterozygous ClinVarID:2893 ClinVarID:2901 CAiD:CA10575472 CAiD:CA115848 PreviousTesting:Full ProteinExpression:Reported PlateletAggregation:Reported inferred_gene_hgnc:6138 inferred_gene_source:CAID ClinGen ITGA2B/ITGB3
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Tags

inferred_gene_hgnc:6138

InheritancePattern:NoInheritanceAssertion

ClinVarID:2893

PreviousTesting:Full

ClinVarID:2901

inferred_gene_source:CAID

ClinGen ITGA2B/ITGB3

Zygosity:CompoundHeterozygous

CaseInfo

Gene:ITGA2B

DiseaseEntity:GlanzmannThrombasthenia

Mutation:Missense

CAiD:CA10575472

Individual

CAiD:CA115848

ProteinExpression:Reported

PlateletAggregation:Reported

Annotators

ClingenBaseline

URL

link.springer.com/article/10.1007/s12185-016-2096-x
academic.oup.com academic.oup.com

Novel GDAP2 pathogenic variants cause autosomal recessive spinocerebellar ataxia-27 (SCAR27) in a Chinese family

1
1. ClingenBaseline 21 Oct 2026
  
  in Baseline Annotations
  
  we report a Chinese male patient carrying novel biallelic GDAP2 variants, c.757C>T (p.Arg253*) and c.1323delC (p.Thr442fs*7), who was diagnosed with SCAR27.
  
  MonDO: MONDO:0032706
  
  Case: Chinese male. Onset at age 30 years with mild dysarthria with progressive worsening.
  
  DiseaseAssertion: Cerebellar ataxia
  
  FamilyInfo: No history of neurological disease and consanguinity was documented in the family. Delivery and perinatal events were unremarkable.
  
  CasePresentingHPOs: HP:0001260, HP:0002141, HP:0002061, HP:0009046 (Dysarthria, Gait imbalance, Lower limb spasticity, Difficulty running
  
  CaseHPOFreeText: Difficulty writing, Increase in bilateral knee reflexes
  
  CaseNOTHPOs: HP:0003487 (Babinski sign)
  
  CasePreviousTesting: His clinical examination displayed cerebellar ataxia with abnormal finger-to-nose and heel-knee-shin tests. Bilateral knee reflexes were symmetrical increased (+++) and Babinski signs were negative. Cranial nerves, muscle strength and sensory examinations were normal. Mild cognitive decline with a Mini-Mental State Examination (MMSE) of 24/30, a Scale for the Assessment and Rating of Ataxia (SARA) score of 17.5/40 and International Cooperative Ataxia Rating Scale (ICARS) score of 46/100. Brain MRI revealed cerebellar atrophy (Fig. 1A).
  
  GenotypingMethod: WES with Sanger confirmation and co-segregation analysis. Genetic testing for spinocerebellar ataxias (SCAs) 1, 2, 3, 6, 7, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) were negative.
  
  VariantEvidence: Wildtype and mutant plasmids were transfected into SH-SY5Y cells. The mRNA level of frameshift variant p.Thr442fs7 was almost same with the level of wild-type, whereas nonsense variant p.Arg253 was even increased, thus they might escape NMD. As a result, p.Gln316 and p.Ser436fs36 mutant GDAP2 proteins were barely detectable, p.Thr442fs7, p.His400fs15 and p.Arg253 generated truncated proteins. Western blot analysis indicated that the GDAP2-Arg253 and GDAP2-Thr442fs*7 were C-terminal deletion mutants.
  
  MultipleGeneVariants:
  
  (1) GeneName: GDAP2
  
  (1) Variant: c.757C>T (p.Arg253*)
  
  (1) ClinVarID or CAID: CA1031554
  
  (1) gnomAD: Total AF 0.00001860, gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-117899096-G-A?dataset=gnomad_r4)
  
  (2) GeneName: GDAP2
  
  (2) Variant: c.1323delC (p.Thr442fs*7)
  
  (2) ClinVarID or CAID: CA2586967196
  
  (2) gnomAD: not found in gnomAD v4.1
  
  MONDO:0032706 CaseInfo Zygosity:CompoundHeterozygous inferred_gene_hgnc:18010 inferred_gene_source:CAID UNC Biocuration Core
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Tags

UNC Biocuration Core

MONDO:0032706

Zygosity:CompoundHeterozygous

inferred_gene_hgnc:18010

CaseInfo

inferred_gene_source:CAID

Annotators

ClingenBaseline

URL

academic.oup.com/brain/article/143/6/e50/5841725
Sep 2026
onlinelibrary.wiley.com onlinelibrary.wiley.com

Longitudinal follow-up of siblings with a discordant Stargardt disease phenotype

1
1. Vibhor 28 Sep 2026
  
  in read_only_demo_group
  
  Patient 2 is the 47-year-old sister of patient 1.
  
  Case#: 47-year-old female, sibling of patient 1.
  
  DiseaseAssertion: Discordant STGD phenotype
  
  FamilyInfo: The mother was found to harbour p.L541V/p.A1038V, and the father carried the p.R811C mutation; both of whom were asymptomatic with normal retinal examination (Fig. 1). ABCA4 screening detected three variants: two variants p.L541V and p.A1038V – commonly co-inherited in a complex allele in STGD (Maugeri et al. 2000) – and a third novel variant p.R881C (Fig. 1). Patient 1 had all three variants
  
  CasePresentingHPOs: HP:0007401, HP:0025010, HP:0011507
  
  CasePhenotypeFreeText: Patient 2 is the 47-year-old sister of patient 1. At initial examination in 1994, she reported a central scotoma. VA was 6/9 in both eyes with bilateral subtle foveal atrophy and perifoveal yellowish-white flecks (Fig. 1). By 2003, foveal atrophy had progressed with more perifoveal flecks (Fig. 1). In 2012, her VA was 6/12 bilaterally, but fundus findings remained stable (Fig. 1). AF imaging demonstrated a mottled signal within the central macula, optical coherence tomography showed outer retinal disruption confined to the central macula
  
  CaseNotHPOs: N/A
  
  CaseNotPhenotypeFreeText: N/A
  
  CasePreviousTesting: The article mentions ABCA4 screen but does not go into detail. However, it does say,”(patient 2) harboured the complex allele (p.L541V/p.A1038V)”
  
  GenotypingMethod: Again only mentioned ABCA4 screening without going into detail.
  
  Variant: NM_000350.3:c.1621C>G and NM_000350.3(ABCA4):c.3113C>T
  
  LegacyVariant: c.1621C>G (p.Leu541Val) and c.3113C>T(p.Ala1038Val)
  
  CAID: CA341280463 and CA119135
  
  gnomeAD: chr1-94063251-G-C and chr1-94043413-G-A
  
  PreviouslyPublished: N/A
  
  AdditionalInfo: Figure 1 provides information about the imaging of patients’ eyes that helps determine phenotype.
  
  Gene:ABCA4 HGNC:34 InheritancePattern:AutosomalRecessive Zygosity:CompoundHeterozygous DiseaseAssertion:DiscordantStargardt'sDisease FovealAtrophy FamilyInfo PerifovealYellowishWhiteFlecks inferred_gene_hgnc:34 inferred_gene_source:hgnc_tag ClinGen ABCA4 Annotations
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Tags

PerifovealYellowishWhiteFlecks

Gene:ABCA4

InheritancePattern:AutosomalRecessive

inferred_gene_hgnc:34

HGNC:34

inferred_gene_source:hgnc_tag

DiseaseAssertion:DiscordantStargardt'sDisease

ClinGen ABCA4 Annotations

FamilyInfo

FovealAtrophy

Zygosity:CompoundHeterozygous

Annotators

Vibhor

URL

onlinelibrary.wiley.com/doi/10.1111/aos.12280
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Clinical and genetic investigations of three Moroccan families with retinitis pigmentosa phenotypes

1
1. Vibhor 27 Sep 2026
  
  in read_only_demo_group
  
  Case 3: RP3.03
  
  Case:RP3,03, male proband with first symptoms as 18 years old. DiseaseAssertion:RP19 FamilyInfo:Proband was born in a consangiuineous family of Moroccan origin. Parents were unaffected. InheritancePattern:AutosomalRecessive CasePresentingHPOs:HP:0007994,HP:0000510,HP:0100014 CaseHPOFreeText:Difficulty with dark adaptation, Fig 4B severe impairment of the entire visual field. Fig 4A Scotopic and photopic ERG traces were altered indicating rod and cone photoreceptor dysfunctions. Macular OCT showed relative preservation of the foveal structure. Epiretinal membrane formation was observed. CaseNOTHPOs:HP:0007667 CaseNOTHPOFreeText:absence of cystic spaces CasePreviousTesting: GenotypingMethod:Whole exome sequencing MultipleGeneVariants: compound heterozygous GeneName:ABCA4 Variant:NM_000350.3(ABCA4):c.5908C>T (p.Leu1970Phe) ClinVarID :7892 gnomAD:0.00362 GeneName:ABCA4 Variant:NM_000350.3(ABCA4):c.6148G>C (p.Val2050Leu) ClinVarID :7884 gnomAD:0.00308
  
  InheritancePattern:AutosomalRecessive Gene:ABCA4 HGNC:34 ClinVarID :7884 ClinVarID :7892 DiseaseEntity:RP19 AlleleOrigin:Germline Zygosity:CompoundHeterozygous NightBlindness FundusAutofluorescence DecreasedERGResponses PigmentaryRetinopathyAttenuatedVessels DecreasedPeripheralVision inferred_gene_hgnc:34 inferred_gene_source:hgnc_tag ClinGen ABCA4 Annotations
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Tags

Gene:ABCA4

ClinVarID :7884

inferred_gene_hgnc:34

HGNC:34

PigmentaryRetinopathyAttenuatedVessels

inferred_gene_source:hgnc_tag

FundusAutofluorescence

AlleleOrigin:Germline

Zygosity:CompoundHeterozygous

NightBlindness

InheritancePattern:AutosomalRecessive

DecreasedERGResponses

DecreasedPeripheralVision

ClinGen ABCA4 Annotations

ClinVarID :7892

DiseaseEntity:RP19

Annotators

Vibhor

URL

pmc.ncbi.nlm.nih.gov/articles/PMC7883928/
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Abnormality in the External Limiting Membrane in early Stargardt Disease

1
1. Vibhor 25 Sep 2026
  
  in read_only_demo_group
  
  5-year-old girl
  
  Case#:5-year-old girl
  
  DiseaseAssertion: Asymptomatic
  
  FamilyInfo: Mother was diagnosed with STGD1 and She was homozygous for a (severe) splice site mutation, IVS 35+2 T>C, Maternal uncle was diagnosed with STGD1. Father passed down the G1961E variant.
  
  CasePresentingHPOs: HP:0030630, HP:0011504
  
  CaseHPOFreeText: The ELM in the central macula appeared thickened with indistinct borders, particularly along its inner border (Fig. 2C), horizontal diameter for the region of thickened ELM was 1113 μm, FAF revealed Bull’s Eye Maculopathy (BEM) (Fig. 2B),
  
  CaseNotHPOs:
  
  CaseNotHPOFreeText: No retinal, vasculature, pigmentary or optic nerve head abnormalities were detected on clinical examination, no focal abnormality observed in the outer nuclear layer (ONL) or RPE (Fig. 2C), There was no FAF evidence of flecks or GA
  
  Genotyping Method:
  
  PreviouslyPublished: No
  
  Variant:NM_000350.3:c.5882G>,
  
  ClinVar:7888
  
  CAID:CA119132
  
  SupplementalData:
  
  Zygosity:CompoundHeterozygous MultipleGeneVariants UnregisteredVariant FamilyInfo ClinVarID:7888 CAID:CA119132 inferred_gene_hgnc:34 inferred_gene_source:CAID ClinGen ABCA4 Annotations
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Tags

MultipleGeneVariants

ClinVarID:7888

inferred_gene_hgnc:34

inferred_gene_source:CAID

UnregisteredVariant

ClinGen ABCA4 Annotations

FamilyInfo

CAID:CA119132

Zygosity:CompoundHeterozygous

Annotators

Vibhor

URL

pmc.ncbi.nlm.nih.gov/articles/PMC4115808/
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Complex Inheritance of ABCA4 Disease: Four Mutations in a Family with Multiple Macular Phenotypes

1
1. Vibhor 25 Sep 2026
  
  in read_only_demo_group
  
  The proband (II-1), a 43-year-old man
  
  Case#: 43-year old man, German descent, onset within first decade of life
  
  DiseaseAssertion: STGD1
  
  FamilyInfo: Family pedigree shown in Figure 1.
  
  CasePresentingHPOs: HP:0011463, HP:0000533, HP:0000580, HP:0030500, HP:0011507, HP:0000548, HP:0000510, HP:0007703, HP:0007663, HP:0000512, HP:0000610
  
  CaseHPOFreeText: Retinal vessels were visibly attenuated.
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: Peripapillary region around the optic nerve had no disease related changes.
  
  Genotyping Method: Illumina MiSeq platform, Array-CGH analysis
  
  PreviouslyPublished: n/a
  
  Variant: NM_000350.3(ABCA4):c.161G>A (p.Cys54Tyr), NM_000350.3(ABCA4):c.4539+2028C>T
  
  ClinVar: 99065, 236116
  
  SupplementalData: n/a
  
  CaseInfo Individual DiseaseEntity:STGD1 MacularFlecks FamilyInfo Zygosity:CompoundHeterozygous InheritancePattern:AutosomalRecessive Funduscopy FundusAutofluorescence ClinVarID:99065 ClinVarID:236116 PigmentaryRetinopathyAttenuatedVessels MacularAtrophy DecreasedCentralVA PeripapillarySparing Chorioretinopathy DecreasedERGResponses inferred_gene_hgnc:1100 inferred_gene_source:ClinVar ClinGen ABCA4 Annotations
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Tags

Chorioretinopathy

DiseaseEntity:STGD1

ClinVarID:236116

PigmentaryRetinopathyAttenuatedVessels

MacularFlecks

ClinVarID:99065

FamilyInfo

FundusAutofluorescence

MacularAtrophy

PeripapillarySparing

Zygosity:CompoundHeterozygous

CaseInfo

DecreasedCentralVA

inferred_gene_hgnc:1100

inferred_gene_source:ClinVar

InheritancePattern:AutosomalRecessive

DecreasedERGResponses

Individual

ClinGen ABCA4 Annotations

Funduscopy

Annotators

Vibhor

URL

pmc.ncbi.nlm.nih.gov/articles/PMC4699863/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Bilateral visual loss, behavioral changes, and overlooking in a young child with stargardt disease: Neurodiagnostic considerations

1
1. Vibhor 24 Sep 2026
  
  in read_only_demo_group
  
  A six-year-old girl with vision loss and prominent behavioral changes and overlooking was presumptively diagnosed as having the Batten disease form of neuronal ceroid lipofuscinosis.
  
  MonDO: MOND:08000406
  
  Case: Female, onset 6 years VA 20/200 OU identify 1 ouf 15 Ishiara cards and overlooking symptom. Presumably diagnosed with Batten disease but found to harbor genetic variant for Stargardt disease.
  
  DiseaseAssertion: Stargardt disease
  
  FamilyInfo: No family history of visual loss in childhood.
  
  "CasePresentingHPOs: HP:0007663, HP:0007988, HP:0030584, HP:0008043, HP:0008001, HP:0030609 (Reduced visual acuity, Macular hypopigmentation, Color vision test abnormality, Retinal arteriolar constriction, Foveal hyperpigmentation, Photoreceptor layer loss on macular OCT"
  
  CaseHPOFreeText: bull's eye lesions, prominent overlooking, hyperreflective granular deposits
  
  CaseNOTHPOFreeText: HP:0001336, HP:0001250, HP:0000648, HP:0000707
  
  CasePreviousTesting: (Myoclonus, Seizure, Optic atrophy, Abnormality of the nervous system
  
  GenotypingMethod: Genetic testing was negative for all mutations known to cause neuronal ceroid lipofuscinosis, but whole exome sequencing showed compound heterozygosity for 2 pathogenic variants in the ABCA4 gene
  
  MultipleGeneVariants:
  
  (1) GeneName: ABCA4
  
  (1) Variant: c.3007C>T, p.Q1003X
  
  (1) ClinVarID or CAID: CA119132
  
  (1) gnomAD: 0.003406 total AF in gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-94008251-C-T?dataset=gnomad_r4)
  
  (2) GeneName: ABCA4
  
  (2) Variant: c.768G>T
  
  (2) ClinVarID or CAID: CA227458
  
  (2) gnomAD: 0.00007930 total AF in gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-94098794-C-A?dataset=gnomad_r4)
  
  CaseInfo Zygosity:CompoundHeterozygous inferred_gene_hgnc:34 inferred_gene_source:CAID ClinGen ABCA4 Annotations
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Tags

ClinGen ABCA4 Annotations

inferred_gene_hgnc:34

Zygosity:CompoundHeterozygous

CaseInfo

inferred_gene_source:CAID

Annotators

Vibhor

URL

ncbi.nlm.nih.gov/pmc/articles/PMC8790276/
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Atypical Retinitis Pigmentosa With Macular Sparing in a Patient With Compound Heterozygous ABCA4 Variants: A Case Report and Diagnostic Challenge

1
1. Vibhor 24 Sep 2026
  
  in read_only_demo_group
  
  A 25‐year‐old male presented to our hospital with a chief complaint of blurred vision in the right eye and significant night vision difficulties (nyctalopia) for 5 years.
  
  Case#:patient, 25, male
  
  DiseaseAssertion:Retinitis Pigmentosa
  
  FamilyInfo:Unaffected brother with no variants, parents each heterozygous for one pathogenic variant in ABCA4
  
  CasePresentingHPOs: HP:0000007, HP:0011462, HP:0007703, HP:0000662, HP:0007641
  
  CaseHPOFreeText: Onset 20 year old. Gradual onset of blurred vision OD, dyschromatopsia. BCVA 1/20 OD 20/20 OS. Optic disc pale, retinal arteries and foveal reflex attenuated. Yellow deposits in perofoveal area and mid-peripheral retina, which showed mottled appearance OU. OCT - thinning of outer nuclear layer and disruption of ellipsoid zone with hyper-reflective flecks. Severe bilateral constriction in visual field. Hypofluorescence of optic disc OU
  
  CaseNotHPOs: n/a
  
  CaseNotHPOFreeText: n/a
  
  Genotyping Method: whole exome (Sanger segregation test)
  
  PreviouslyPublished: n/a
  
  Variant: NM_000350.3:c.4793C>A; NM_000350.3:c.1769A>G
  
  ClinVar: 99321
  
  CAID: CA341279788
  
  SupplementalData: n/a
  
  InheritancePattern:AutosomalRecessive DiseaseEntity:IRD DiseaseEntity:RP AlleleOrigin:Germline Zygosity:CompoundHeterozygous CAID:CA341279788 ClinVarID: 99321 RPEMottling NightBlindness OpticnervePallor inferred_gene_hgnc:34 inferred_gene_source:CAID ClinGen ABCA4 Annotations
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Tags

NightBlindness

DiseaseEntity:IRD

CAID:CA341279788

InheritancePattern:AutosomalRecessive

inferred_gene_hgnc:34

DiseaseEntity:RP

inferred_gene_source:CAID

ClinVarID: 99321

ClinGen ABCA4 Annotations

OpticnervePallor

AlleleOrigin:Germline

Zygosity:CompoundHeterozygous

RPEMottling

Annotators

Vibhor

URL

pmc.ncbi.nlm.nih.gov/articles/PMC12740048/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies

1
1. Vibhor 23 Sep 2026
  
  in read_only_demo_group
  
  In case 71674, diagnosed with arRD, along with a recurrent nonsense mutation (p.Trp663*, HGMD Accession = {"type":"entrez-nucleotide","attrs":{"text":"CM003370","term_id":"909078994","term_text":"CM003370"}}CM003370), a novel splice-site variant was identified (c.2160 + 1 G > T) (Fig. 3a). This variant is predicted to lead to skipping of exon 14 in the ABCA4 transcript. The patient inherited one mutant allele from each parent.
  
  Patient 71674: Female, Swiss, 13 years old. bi-allelic variants in ABCA4, diagnosed with Retinal dystrophy DD: Retinitis pigmentosa
  
  Figure 3: Segregation analysis performed on family samples GenotypingMethod: Whole exome sequencing performed on HiSeq2000 and NextSeq500 (252 genes)
  
  Multiple Variants: VPS13B NM_017890.4:c.897 8A>G:p.Asn2993Ser Heterozygous CM041280
  
  PCDH15 NM_001142763.1:c. 4329_4337del:p.Pro 1446_Pro1448del Heterozygous
  
  DHX38 NM_014003.3:c.366 2C>T:p.Thr1221Met Heterozygous
  
  USH1G NM_173477.4:c.310 A>G:p.Met104Val Heterozygous
  
  CAID:CA16042332 PMID:27353947 CaseInfo Zygosity:CompoundHeterozygous inferred_gene_hgnc:34 inferred_gene_source:CAID ClinGen ABCA4 Annotations
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PMID:27353947

ClinGen ABCA4 Annotations

inferred_gene_hgnc:34

Zygosity:CompoundHeterozygous

CaseInfo

CAID:CA16042332

inferred_gene_source:CAID

Annotators

Vibhor

URL

ncbi.nlm.nih.gov/pmc/articles/PMC4926080/
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

CLINICAL CHARACTERIZATION OF STARGARDT DISEASE PATIENTS WITH THE p.N1868I ABCA4 MUTATION

1
1. Vibhor 21 Sep 2026
  
  in read_only_demo_group
  
  The proband of Family #1 (Patient #1, II:1 in pedigree Figure 1A)
  
  Case#: Male, Family #1, Patient #1, II:1 in pedigree
  
  DiseaseAssertion: Hypomorphic Stargardt disease
  
  FamilyInfo: Paternal female cousin also has hypomorphic Stargardt disease and both of them carry the complex allele p.[L541P; A1038V] and p.N1868I. Additionally, their paternal aunt was diagnosed with Stargardt disease. This information can be found on Fig.1.
  
  CasePresentingHPOs: HP:0000622, HP:0025010
  
  CaseHPOFreeText: This proband developed blurred vision at age 30. The foveal atrophy affects the left eye. In the first visit at 33.9 years old patient presents with 20/25-3 Snellen VA OD, 20/70-2 Snellen VA OS, 0.16 LogMAR VA OD, 0.58 LogMAR VA OS, and stage 1. In the last visit at age 40.7, the patient had a 20/40-2 Snellen VA OD, a 10/80-1 Snellen VA OS, 0.34 LogMAR VA OD, 0.92 LogMAR VA OS, and was now in stage 2. In a Goldmann Visual Field test, they found central scotomas II4e; mild-moderate constriction II2e.
  
  CaseNotHPOs: N/a
  
  CaseNotHPOFreeText: The proband maintained some relative foveolar sparing in his right eye and had a BCVAs of 20/4022 (test done at 40 years old).
  
  Genotyping Method: Genetic testing was performed at Columbia University. It was not stated which method this proband underwent, so the genetic testing could have been one of the following: "The entire ABCA4 gene locus was sequenced in 17 patients; the ABCA4 gene, including all exons and intron/exon boundaries were sequenced in 4 patients. In the remaining 6 cases representing family members, only targeted testing was performed."
  
  PreviouslyPublished: N/a
  
  **Variant: ** M1) NM_000350.3(ABCA4):c.5603A>T M2) NM_000350.3(ABCA4):c.1622T>C (p.Leu541Pro)
  
  ClinVar: M1) 99390 M2) 99067
  
  CAID: N/a
  
  gnomAD: M1) The highest minor allele frequency was 0.05787 (https://www.ncbi.nlm.nih.gov/clinvar/variation/99390/) M2) The highest minor allele frequency was 0.00017 (https://www.ncbi.nlm.nih.gov/clinvar/variation/99067/)
  
  SupplementalData: Table 1. provided patient information for those with p.N1868I ABCA4 Stargardt disease and the associated ABCA4 mutations. Fig.1. shows the pedigrees of the families. Fig.3. shows Macular SD-OCT line profiles for some of the patients. Table 2. describes the onset/symptoms of the patients with p.N1868I ABCA4 Stargardt Disease. Table 3. shows Visual Acuity and Stage at Baseline and Most Recent Follow-up in Patients With p.N1868I ABCA4 Stargardt Disease. Fig.4. shows BCVA better eye vs Duration since first examination for the patients. Table 4. shows clinical findings in the patients.
  
  Gene:ABCA4 HGNC:34 InheritancePattern:AutosomalRecessive HypomorphicSTGD AlleleOrigin:Somatic Zygosity:CompoundHeterozygous FamilyInfo inferred_gene_hgnc:34 inferred_gene_source:hgnc_tag ClinGen ABCA4 Annotations
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Tags

HypomorphicSTGD

Gene:ABCA4

InheritancePattern:AutosomalRecessive

inferred_gene_hgnc:34

HGNC:34

AlleleOrigin:Somatic

inferred_gene_source:hgnc_tag

ClinGen ABCA4 Annotations

FamilyInfo

Zygosity:CompoundHeterozygous

Annotators

Vibhor

URL

pmc.ncbi.nlm.nih.gov/articles/PMC6548695/pdf/nihms-1032320.pdf
www.sciencedirect.com www.sciencedirect.com

A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease

1
1. Vibhor 21 Sep 2026
  
  in read_only_demo_group
  
  Patient 4, a 33-year-old Caucasian woman, presented in July 1998 with a gradual decline in visual acuity over the last 9 years and a best-corrected visual acuity of 20/300 in both eyes.
  
  Case#: Patient 4, Female, Caucasian, 33yo
  
  DiseaseAssertion: STGD1
  
  FamilyInfo: One of eight siblings; four affected. Disease segregates with ABCA4 variants consistent with autosomal recessive inheritance. Parents are deceased and can't be tested.
  
  CasePresentingHPOs: HP:0007663, HP:0007754, HP:0025147, HP:0007924, HP:0011507
  
  CaseHPOFreeText: gradual decline in visual acuity over 9 years, BCVA 20/300 OU, bilateral beaten-bronze appearance of the macula, numerous perimacular yellow flecks, fluorescein angiography showing hyperfluorescence in the posterior pole and dark choroid in the periphery
  
  CaseNotHPOs: N/A
  
  CaseNotHPOFreeText: absence of central hypofluorescence on fluorescein angiography (present in affected siblings but not this patient)
  
  Genotyping Method: SSCP analysis; Taq Dyedeoxy Terminator Cycle Sequencing kit
  
  PreviouslyPublished: N/A
  
  Variant: NM_000350.3(ABCA4):c.2588G>C (p.Gly863Ala), NM_000350.3(ABCA4):c.161G>A (p.Cys54Tyr)
  
  ClinVar: ClinVarID:7879, ClinVarID:99065
  
  CAID: N/A
  
  SupplementalData: Segregation and sequencing data (Figures 1, 4)
  
  Gene:ABCA4 HGNC:34 DiseaseEntity:STGD1 InheritancePattern:AutosomalRecessive ClinVarID:7879 ClinVarID:99065 Zygosity:CompoundHeterozygous AlleleOrigin:Germline BeatenBronzeAppearance DecreasedCentralVA MacularAtrophy MacularFlecks FamilyInfo CaseInfo Individual inferred_gene_hgnc:34 inferred_gene_source:hgnc_tag ClinGen ABCA4 Annotations
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Tags

Gene:ABCA4

DiseaseEntity:STGD1

inferred_gene_hgnc:34

HGNC:34

BeatenBronzeAppearance

inferred_gene_source:hgnc_tag

MacularFlecks

ClinVarID:99065

MacularAtrophy

FamilyInfo

ClinVarID:7879

Zygosity:CompoundHeterozygous

AlleleOrigin:Germline

CaseInfo

DecreasedCentralVA

InheritancePattern:AutosomalRecessive

Individual

ClinGen ABCA4 Annotations

Annotators

Vibhor

URL

sciencedirect.com/science/article/pii/S0002939499002366

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