Case#: 15 year old, female

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0000225, 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: 953046

CAID: CA399802348

Variant: NM_000419.5:c.1651C>T

GnomAD: Highest in East Asian population at a rate of 0.00005045 (1/19820)

Allele 2:

ClinVar: 225393

CAID: CA290947544

Variant: NM_000419.5:c.2333A>C

GnomAD: East Asian: 0.0001087 (2/18394)

ExpressionEvidence:Flow Cytometry of platelet integrin: 7.7% B3 expression, .82% A2B expression

Case#: 39 year old, male

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: 2891

CAID: CA115831

Variant: NM_000419.5:c.2621T>G

GnomAD: European at rate of (9494/21600) 0.4395 and East Asian at 0.4327

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: 83.9% B3 expression, 4.4% A2B expression

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

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

Case3: Male, 10 years old, Korean

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Figure 1 shows haplotype analysis

CasePresentingHPOs: HP:0001342

(Cerebral hemorrhage)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analyses revealed decreased expression at 7.2%/5.0% of the normal amount of CD41/CD61

PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists

CasePreviousTesting: Polymerase chain reaction for all exons ofITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 forITGA2Band NM_000212.2 and NP_000203.2 for ITGB3.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.975del

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544 and CA915940385

gnomAD: MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-42453691-T-G

Case4: Male, 4 years old, Korean

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Figure 1 shows haplotype analysis

CasePresentingHPOs: HP:0000978, HP:0000967

(Easy bruising, petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analyses revealed decreased expression at a level of 7.5%(type II GT)

PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists

CasePreviousTesting: Polymerase chain reaction for all exons of ITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 for ITGA2B and NM_000212.2 and NP_000203.2 for ITGB3.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 225393 and 2892

CAiD: CA290947544 and CA115834

gnomAD: MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-42453691-T-G and MAF in the East Asian population is 0.0002176 http://gnomad.broadinstitute.org/variant/17-42457372-G-A

Supplementary Tables 1 and 2 combined information:

Case16: GT16, Male, 31 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per supplementary table 1; however very minimal information

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

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.2267+1G>T no protein coding sequence available

LegacyVariant: N/A

ClinVar: 225393 (p.Gln778Pro)

CAiD: CA290947544 (p.Gln778Pro) and CA399798124 for (c.2267+1G>T )

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case9: GT9, Female, 25 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000421, HP:0000132

(Epistaxis, 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.2333A>C (p.Gln778Pro)

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case24: GT24, Female, 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, HP:0000225

(Bruising, purpura, ecchymosis, epistaxis, gingival bleeding)

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 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: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.1750C>T (p.Arg584Ter) This article is still being done-Meera)

LegacyVariant: N/A

ClinVar: 225393 (p.Gln778Pro) and 2892 (p.Arg584Ter)

CAiD: CA290947544 (p.Gln778Pro) and CA115834 (p.Arg584Ter)

gnomAD: MAF in East Asian population: 0.0002176 (p.Arg584Ter) https://gnomad.broadinstitute.org/variant/17-42457372-G-A and MAF in East Asian population for p.Gln778Pro 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Supplementary Tables 1 and 2 combined information:

Case27: GT27, Male, 29 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per Table 1; however, very minimal information

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364

(Bruising, purpura, ecchymosis)

CaseHPOFreeText: Post traumatic hemorrhage

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 (p.Gln778Pro) This article is not completed-Meera

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: MAF in East Asian population: 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Supplementary Tables 1 and 2 combined information:

Case14: GT14, Female, 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, 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

Variant: NM_000419.3:c.2333A>C

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: N/A

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

Supplementary Tables 1 and 2 combined information:

Case12: GT12, Male, 10 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Family history available per Table 1; however, no further information given

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: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro)

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: N/A

Case#: Patient ID 9, Female, Korean

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0001892, HP:0000978

Abnormal Bleeding, Bruising susceptibility

PlateletAgreggation: Decreased response to ADP, COL, EPI, normal response to RIS

GenotypingMethod: Targeted Exome sequencing followed by Whole exome sequencing performed.

Allele 1:

ClinVar:Not Found

CAID: CA2573131754

Variant: NM_000419.5:c.2390del

GnomAD: Not Found

Allele 2

ClinVar: 225393

CAID:CA290947544

Variant: NM_000419.5:c.2333A>C

GnomAD:East Asian at rate of 0.0001087 (2/18394)

ExpressionEvidence: Decreased CD41 expression by flow cytometry

Case13: (Proband CabGT-13) Male, age not specified, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed <5% of 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: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro)

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD MAF in the East Asian population is 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Case4: Female, 35 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A per Table 1

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Prolonged ivy bleeding times, bleeding diathesis since early childhood

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Surface expression of αIIbβ3 was analyzed by flow cytometry which was 10-20% of normal

PlateletAggregation: Aggregation in response to ADP, epinephrine and collagen was absent but normal in response to ristocetin

CasePreviousTesting: Nucleotide sequences of the αIIb and β3 coding regions were determined by direct sequencing of RT-PCR products from platelet RNA.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro)

LegacyVariant: (p.Gln747Pro)

ClinVar: 225393

CAiD: CA290947544

gnomAD: MAF in the East Asian population is 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Case3: Female, 32 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A per Table 1

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Prolonged ivy bleeding times, bleeding diathesis since early childhood

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Surface expression of αIIbβ3 was analyzed by flow cytometry which was 10-20% of normal

PlateletAggregation: Aggregation in response to ADP, epinephrine and collagen was absent but normal in response to ristocetin

CasePreviousTesting: Nucleotide sequences of the αIIb and β3 coding regions were determined by direct sequencing of RT-PCR products from platelet RNA.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro)

LegacyVariant: (p.Gln747Pro)

ClinVar: 225393

CAiD: CA290947544

gnomAD: MAF in the East Asian population is 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G