Case: Patient 11 (Family E), male, 11yo

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 = 220, PFA 100 sec = >300, SPA % = 11.3, MADR mg/mL = 0.3, VWF:Ag U/dL = 28.8, VWF:CB U/dL = 28.4, VWF:CB ratio = 0.98, VWF:RCo U/dL = 23.0, VWF:RCo ratio = 0.80, Platelet VWF U/dL = 54.1, FVIII U/dL = 51.5, BAT F/M = 5

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.4021C>T (p.Arg1341Trp)

HGVS: NM_000552.4(VWF):c.4021C>T (p.Arg1341Trp)

ClinVarID: 100316; https://www.ncbi.nlm.nih.gov/clinvar/variation/100316/

CAID: NA

gnomAD: MAF = 0.00008674 (3/34586 alleles) in the Latino/Admixed American population; https://gnomad.broadinstitute.org/variant/12-6128563-G-A?dataset=gnomad_r2_1

Case UZ043: 8 year old male (row 44 supplemental table)

DiseaseAssertion: type 2B VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 29.3; vWF:GPIbR (%) = 13.6; Act/Ag ratio = 0.46; FVIII:C (%) = 68.1; Platelets (x10^9/L) = 176

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4021C>T p.Arg1341Trp

HGVS:

ClinVarID: 100316

CAID:

gnomAD: 0.00001859 (30 in 1613842) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019397-G-A?dataset=gnomad_r4