Case: Patient 4, Family C (Table 1.), F/38, Afro-Caribbean

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs:

CaseHPOFreeRext: BAT = 16, FVIII:C (IU/dL) = NA, VWF:Ag (IU/dL) = 40, VWF:Act (IU/dL) = 36

CaseNOTHPOs:

CaseNOTHPOFreeText: Blood group A

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.2365A > G p.(Thr789Ala)

HGVS: NM_000552.5:c.2365A>G (p.Thr789Ala)

ClinVarID: 256659

CAID: CA6403090

gnomAD: MAF of 0.5793 (43409/74928 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/12-6044368-T-C?dataset=gnomad_r4

Variant: c.2385T > C p.(Tyr795 =)

HGVS: NM_000552.5:c.2385T>C (p.Tyr795=)

ClinVarID: 256660

CAID: CA6403087

gnomAD: MAF of 0.5788 (43385/74952 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/12-6044348-A-G?dataset=gnomad_r4

Variant: c.4019T > C p.(Leu1340Arg)

the paper incorrectly lists the amino acid change as Leu1340Arg but it should be Leu1340Pro

HGVS: NM_000552.5:c.4019T>C

ClinVarID: 3061402

CAID: CA383505745

gnomAD:

Variant: c.4457C > T p.(Ser1486Leu)

HGVS: NM_000552.5:c.4457C>T (p.Ser1486Leu)

ClinVarID: 560630

CAID: CA6402527

gnomAD: MAF of 0.009120 (684/74998 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/12-6018961-G-A?dataset=gnomad_r4

Variant: c.6187C > T p.(Pro2063Ser)

HGVS: NM_000552.5:c.6187C>T (p.Pro2063Ser)

ClinVarID: 100436

CAID: CA202650

gnomAD: MAF of 0.04780 (4353/91066 alleles) in Africa/African American population https://gnomad.broadinstitute.org/variant/12-5994484-G-A?dataset=gnomad_r4

Variant: c.7059G > C p.(Glu2353Ser)

paper incorrectly lists amino acid change as Glu2353Ser but it should be Glu2353Asp

HGVS: NM_000552.5:c.7059G>C

ClinVarID: 993253

CAID: CA6401794

gnomAD: MAF of 0.006101 (458/75068 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5983172-C-G?dataset=gnomad_r4