Case 16: 1 year old female, study ID UZ052 in supplemental table

DiseaseAssertion: type 3 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 1.5; vWF:GPIbR (%) = 0.6; Act/Ag ratio = 0.40; FVIII:C (%) = 12.2; Platelets (x10^9/L) = 369

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.421G>A p.Asp141Asn

HGVS:

ClinVarID: 100338

CAID:

gnomAD: 6.195e-7 (1 in 1614092) no homozygotes https://gnomad.broadinstitute.org/variant/12-6110483-A-G?dataset=gnomad_r4

MultipleGeneVariants:

VWF variant

Variant: c.7940C>T p.Thr2647Met p.Thr2647Met

ClinVarID: 100487

gnomAD: 0.004007 (6468 in 1614124) 21 homozygotes https://gnomad.broadinstitute.org/variant/12-5953542-G-A?dataset=gnomad_r4

Case: IP #1

DiseaseAssertion: type 2A (IIC) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 11.4; VWF:Ac [IU/dL] = 4; 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.421G>A p.Asp141Asn

HGVS:

ClinVarID: 100338

CAID:

gnomAD: absent