Case: Case 2, male, newborn

DiseaseAssertion: VWD2B

FamilyInfo: First child of consanguineous parents (first cousins), no family history of bleeding, search of maternal platelet autoantibodies was negative; parents had VWF measurements showed decreased VWF:RCo, ratio FVIII:C/VWF:Ag < 0.5, and enhanced RIPA

ParentalGenotype(s): both parents heterozygous for both variants

CasePresentingHPOs: HP:0012330, HP:0001873, HP:0000967, HP:0030129

(Pyelonephritis, thrombocytopenia, petechiae, impaired ristocetin cofactor assay activity)

CaseHPOFreeText: born at 40wks, thrombocytopenia: 5 GL−1 at birth, platelets clumps in citrate tube, normal platelet morphology, no platelet incompatibility between the mother and the child in HPA groups 1, 3, 5, and 15, Allo- and autoantibodies on the mother and child and cross-match between father and mother serum were negative; bone marrow aspiration showed hyperplasia of megakaryocyte line, with all stages of maturation, consistent with peripheral origin, normal development; VWF:RCo = 13 IU dL−1, VWF:Ag = 47 IU dL−1, VWF:RCo /VWF:Ag= 0.3, FVIII:C = 22 IU dL−1, FVIII/VWF:Ag= 0.6, VWF:FVIII = 10 IU dL−1< RIPA analysis could not be performed

CaseNOTHPOs: HP:0032169, HP:0001892

(infection, abnormal bleeding)

CaseNOTHPOFreeText: DIC

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 20 and 28 of VWF gene

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.4010C>T (p.Pro1337Leu); exon 28, homozygous

HGVS: NM_000552.4(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/

CAID: NA

gnomAD: MAF = 0.00005440 (1/18384 alleles) in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A?dataset=gnomad_r2_1

Variant 2: c.2561G>A (p.Arg854Gln); exon 20; homozygous

HGVS: NM_000552.4(VWF):c.2561G>A (p.Arg854Gln)

ClinVarID: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/

CAID: NA

gnomAD: MAF = 0.005692 (143/25122 alleles, 4 homozygotes) in European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6143978-C-T?dataset=gnomad_r2_1

Case: 2B-4

DiseaseAssertion: VWD2B

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: AcuStar RCo/Ag = 0.55; AcuStar CB/Ag = 0.44; ELISA CB/Ag = 0.44

CaseHPOFreeText:

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: not described

PreviouslyPublished: 1373334

Gene: VWF

Variant: c.4010C>T (p.Pro1337Leu)

HGVS: NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/?new_evidence=false

CAID:

gnomAD: MAF = 0.00005440 in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A

Case: 2B-3

DiseaseAssertion: VWD2B

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: AcuStar RCo/Ag = 0.12; AcuStar CB/Ag = 0.09; ELISA CB/Ag = 0.56

CaseHPOFreeText:

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: not described

PreviouslyPublished: 1373334

Gene: VWF

Variant: c.4010C>T (p.Pro1337Leu)

HGVS: NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/?new_evidence=false

CAID:

gnomAD: MAF = 0.00005440 in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A

Case: 2B-1

DiseaseAssertion: VWD2B

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: AcuStar RCo/Ag = 0.41; AcuStar CB/Ag = 0.49; ELISA CB/Ag = 0.40

CaseHPOFreeText:

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: not described

PreviouslyPublished: 1373334

Gene: VWF

Variant: c.4010C>T (p.Pro1337Leu)

HGVS: NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/?new_evidence=false

CAID:

gnomAD: MAF = 0.00005440 in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A

Case: 2B-6

DiseaseAssertion: VWD2B

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: AcuStar RCo/Ag = 0.66; AcuStar CB/Ag = 0.69; ELISA CB/Ag = 0.71

CaseHPOFreeText:

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: not described

PreviouslyPublished: 1373334

Gene: VWF

Variant: c.4010C>T (p.Pro1337Leu)

HGVS: NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/?new_evidence=false

CAID:

gnomAD: MAF = 0.00005440 in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A

Case: 2B-5

DiseaseAssertion: VWD2B

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: AcuStar RCo/Ag = 0.32; AcuStar CB/Ag = 0.19; ELISA CB/Ag = 0.38

CaseHPOFreeText:

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: not described

PreviouslyPublished: 1373334

Gene: VWF

Variant: c.4010C>T (p.Pro1337Leu)

HGVS: NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/?new_evidence=false

CAID:

gnomAD: MAF = 0.00005440 in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A

Case: 2B-2

DiseaseAssertion: VWD2B

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: AcuStar RCo/Ag = 0.62; AcuStar CB/Ag = 0.50; ELISA CB/Ag = 0.47

CaseHPOFreeText:

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: not described

PreviouslyPublished: 1373334

Gene: VWF

Variant: c.4010C>T (p.Pro1337Leu)

HGVS: NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/?new_evidence=false

CAID:

gnomAD: MAF = 0.00005440 in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A