24 I
Case: Patient 24, Family I (Table 1.), F/92, Afro-Caribbean
DiseaseAssertion: VWD2A (IIE)
FamilyInfo: Patient 13 (F/65, Afro-Caribbean), Patient 21 (F/97, Afro-Caribbean), Patient 22 (F/67, Afro-Caribbean), Patient 23 (F/86, Afro-Caribbean), Patient 25 (F/62, Afro-Carribean) also from Family I. (Table 1.)
ParentalGenotype(s): NA
CasePresentingHPOs:
CaseHPOFreeRext: BAT =3, FVIII:C (IU/dL) = 61, VWF:Ag (IU/dL) = 30, VWF:Act (IU/dL) = 29
CaseNOTHPOs:
CaseNOTHPOFreeText: Blood group B+
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.1530G > A, p.(Val510 =) p.
HGVS: NM_000552.5:c.1530G>A (p.Val510=)
ClinVarID:
CAID: CA6403368
gnomAD: MAF of 0.00002198 (2/91004 alleles) in South Asian population https://gnomad.broadinstitute.org/variant/chr12-6062957-C-T?dataset=gnomad_r4
Variant: c.1892C > T, p.(Ala631Val)
HGVS: NM_000552.5:c.1892C>T (p.Ala631Val)
ClinVarID: 422844
CAID: CA6403245
gnomAD: MAF of 0.001908 (137/71810 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6056910-G-A?dataset=gnomad_r4
Variant: c.2220G > A, p.(Met740Ile)
HGVS: NM_000552.5:c.2220G>A (p.Met740Ile)
ClinVarID: 100206
CAID: CA201316
gnomAD: MAF of 0.1816 (13626/75022 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6046784-C-T?dataset=gnomad_r4
Variant: c.2451T > A, p.(His817Gln)
HGVS: NM_000552.5:c.2451T>A (p.His817Gln)
ClinVarID: 100224
CAID: CA228345
gnomAD: MAF of 0.1150 (8626/75016 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6036483-A-T?dataset=gnomad_r4
Variant: c.3258C > T, p.(Tyr1086 =)
HGVS: NM_000552.5:c.3258C>T (p.Tyr1086=)
ClinVarID: 256664
CAID: CA6402788
gnomAD: MAF of 0.1284 (9131/71128 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-6023752-G-A?dataset=gnomad_r4
Variant: c.3445T > C, p.(Cys1149Arg)
HGVS: NM_000552.5:c.3445T>C (p.Cys1149Arg)
ClinVarID: 309
CAID: CA228410
gnomAD: MAF of 0.000003160 (1/316464 alleles) in European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr12-6022833-A-G?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
Variant: c.6554G > A, p.(Arg2185Gln)
HGVS: NM_000552.5:c.6554G>A (p.Arg2185Gln)
ClinVarID: 100443
CAID: CA228748
gnomAD: MAF of 0.1927 (14427/74878 alleles) in African/African American population https://gnomad.broadinstitute.org/variant/chr12-5993906-C-T?dataset=gnomad_r4