Case: P76, Chinese, male, 21yo

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 3; VWF:Ag (%) = 4.7, VWF:RCo (%) = 5.4, FVIII:C (%) = 27.2, VWF:CB (%) = 5.5, VWFpp (%) = 4.3, VWF:RCo/VWF:Ag = 1.1, VWF:CB/VWF:Ag = 1.2, VWFpp/VWF:Ag = 0.9, FVIII:C/VWF:Ag = 5.8, RIPA (1.2 mg/ml, %) = 73.4

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: Exon1-exon5 del - Unregistered Variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Variant 2: c.7464C>T (p.Gly2488=) - reported to be a splice site variant

HGVS: NM_000552.4(VWF):c.7464C>T (p.Gly2488=)

ClinVarID: 619755; https://www.ncbi.nlm.nih.gov/clinvar/variation/619755/

CAID: NA

gnomAD: MAF = 0.000008799 (1/113644 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6080849-G-A?dataset=gnomad_r2_1

Case: P1, female, 36yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147, HP:0030129, HP:0030130

(Reduced quantity of VWF, Impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity)

CaseHPOFreeText: bleeding score = 7; VWF:Ag (%) = 22, VWF:RCo(%) = 11, VWF:RCo/VWF:Ag ratio = 0.50, VWF:CIIIB (%) = 19, VWF:CIIIB/VWF:Ag ratio = 0.86, VWF:CVIB (%) = 13, VWF:CVIB/VWF:Ag ratio = 0.59

CaseNOTHPOs: HP:0030132

(Absence of large von Willebrand factor multimers)

CaseNOTHPOFreeText: NA

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.3944G>A (p.Arg1315His)

HGVS: NM_000552.4(VWF):c.3944G>A (p.Arg1315His)

ClinVarID: 100311; https://www.ncbi.nlm.nih.gov/clinvar/variation/100311/

CAID:

gnomAD: MAF = 0.0001633 (1/6124 alleles) in "Other" population; https://gnomad.broadinstitute.org/variant/12-6128640-C-T?dataset=gnomad_r2_1

Variant 2: c.7464C>T (p.Gly2488=)

HGVS: NM_000552.4(VWF):c.7464C>T (p.Gly2488=)

ClinVar: 619755; https://www.ncbi.nlm.nih.gov/clinvar/variation/619755/

gnomAD: MAF = 0.000008799 (1/113644 alleles) in European (Non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6080849-G-A?dataset=gnomad_r2_1

Case: IP #3 (also in row 1 splice variants table 6)

DiseaseAssertion: Type 2A (IIC) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 49; VWF:Ac [IU/dL] = n/a; FVIII:C [IU/dL] = n/a

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.1110-6_1110-5insC

HGVS: NM_000552.5:c.1110-6dup p.?

ClinVarID: 507028

CAID:

gnomAD: absent