Case: Patient 3, Family B (Table 1.), M/30, Afro-Caribbean

DiseaseAssertion: VWD2A (IIE)

FamilyInfo: Patient 5 (F/47, Afro-Caribbean) from same family B (Table 1.).

ParentalGenotype(s): NA

CasePresentingHPOs:

CaseHPOFreeRext: BAT = 4, FVIII:C (IU/dL) = 14, VWF:Ag (IU/dL) = 10, VWF:Act (IU/dL) = 4.9

CaseNOTHPOs:

CaseNOTHPOFreeText: Blood group O+

CasePreviousTesting:

GenotypingMethod: All samples were analyzed by captured-based high throughput sequencing which was performed with a custom-design of the VWF gene provided by Twist BioScience (San Francisco, USA). It comprised all 52 exons, intronic flanking regions, promoter and 3’UTR region of the VWF gene. Libraries were prepared by using the Twist NGS target enrichment solution (Twist BioScience) according to the manufacturer protocol. Samples were analyzed on a NovaSeq 6000 sequencer (Illumina) with a median read depth of 2500X by using the 300-cycle S1 NovaSeq 6000seq reagent kit with 150-bp paired-end reads. The raw data were analyzed with Mutect21 and Vardict2 tools. The inhouse NGSreport software (CHU Lille) was used for data visualization, sequences check and conservation of variants with high quality metrics. In some cases, patients genomic DNA was screened for sequence variations (large deletions, insertions and duplications) by Multiplex Ligation-dependent Probe Amplification (MCR Holland).

PreviouslyPublished: NA

Gene: VWF

Variant: c.2739A > C, p.(Gly913 =)

HGVS: NM_000552.5:c.2739A>C p.(Gly913=)

ClinVarID: 1336650

CAID: CA6402959

gnomAD: MAF of 0.003374 (253/74996 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/12-6031525-T-G?dataset=gnomad_r4

Variant: c.2815G > A, p.(Gly939Arg)

HGVS: NM_000552.5:c.2815G>A (p.Gly939Arg)

ClinVarID: 2500546

CAID: CA6402950

gnomAD: MAF of 0.0009595 (72/75038 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/12-6031449-C-T?dataset=gnomad_r4

Variant: c.3101_3103delCCA (p.Thr1034del)

HGVS: NM_000552.5:c.3101_3103delCCA (p.Thr1034del)

ClinVarID: 802812

CAID: CA6402852

gnomAD: MAF of 0.01532 (1150/7504 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6025910-CTGG-C?dataset=gnomad_r4

Variant: c.4138A > G, p.(Ile1380Val)

HGVS: NM_000552.5:c.4138A>G (p.Ile1380Val)

ClinVarID: 310063

CAID: CA6402595

gnomAD: MAF of 0.1184 (8878/74958 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019280-T-C?dataset=gnomad_r4

Variant: c.4304A > G p.(Asn1435Ser)

HGVS: NM_000552.5:c.4304A>G (p.Asn1435Ser)

ClinVarID: 310062

CAID: CA6402552

gnomAD: MAF of 0.1124 (8427/74964 alleles) in Africa/African American population https://gnomad.broadinstitute.org/variant/chr12-6019114-T-C?dataset=gnomad_r4

Variant: c.4414G > C p.(Asp1472His)

HGVS: NM_000552.5:c.4414G>C (p.Asp1472His)

ClinVarID: 256679

CAID: CA6402534

gnomAD: MAF of 0.5076 (38011/74882 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6019004-C-G?dataset=gnomad_r4