Case: IP #27 in type 2N VWD sub-cohort

DiseaseAssertion: type 2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 42; VWF:Ac [IU/dL] = 44; FVIII:C [IU/dL] = 69

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.3673T>G p.Cys1225Gly

HGVS:

ClinVarID: 100272

CAID:

gnomAD: absent

Case: 8 (also in row 21 table 6)

DiseaseAssertion: type 2A/2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 16; VWF:Ac [IU/dL] = 8; FVIII:C [IU/dL] = 12

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.2561G>A p.Arg854Gln

HGVS:

ClinVarID: 296

CAID:

gnomAD: 0.004956 (8000 in 1614214) 26 homozygotes https://gnomad.broadinstitute.org/variant/12-6034812-C-T?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.4811T>A p.Val1604Asp

CAID: CA383499144

gnomAD: absent

Case: IP #24 in type 2N VWD sub-cohort (also in row 5 splice variants table 6)

DiseaseAssertion: type 2N/1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032441 - blood group AB

CaseHPOFreeRext: VWF:Ag [IU/dL] = 42; VWF:Ac [IU/dL] = 34; FVIII:C [IU/dL] = 16

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.2561G>A p.Arg854Gln

HGVS:

ClinVarID: 296

CAID:

gnomAD: 0.004956 (8000 in 1614214) 26 homozygotes https://gnomad.broadinstitute.org/variant/12-6034812-C-T?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.6798+2T>A

ClinVarID: 1803122

gnomAD: absent

Case#: Male, 31<br /> DiseaseAssertion: VWD 2N<br /> FamilyInfo: A younger brother with mild HA, sister with normal VWF levels, no other famile members with bleeding disorders<br /> ParentalGenotype: <br /> CasePresentingHPOs: HP:0000421 (epistaxis), HP:0007420 (spontaneous hematoma)<br /> CaseHPOFreeText: Soft tissue bleeding, VWF:Ag 80%, VWF:RCo 60%, normal VWF multimer pattern<br /> CaseNotHPOs:<br /> CaseNotHPOFreeText: <br /> CasePreviousTesting: Genotyping using Next Gen screening, by Sanger sequence screening of all 26 exons of F8 gene, by a multiplex ligation-dependent probe affinity assay, and by a VWF:FVIII binding assay<br /> Gene: VWF<br /> Variant: c2390T>G in exon 18<br /> ClinVar:<br /> CAID: gnomAD:

Case: P27, Chinese, female, 3yo

DiseaseAssertion: VWD2N

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type B blood, bleeding score = 6; VWF:Ag (%) = 9.5, VWF:RCo (%) = 8.9, FVIII:C (%) = 6.5, VWF:CB (%) = 6.9, VWFpp (%) = 10.8, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.7, VWFpp/VWF:Ag = 1.1, FVIII:C/VWF:Ag = 0.7, VWF: FVIIIB (%) = 0.0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.2396G>A (p.Cys799Tyr)

HGVS: NM_000552.5:c.2396G>A (p.Cys799Tyr)

ClinVarID: NA

CAID: CA232300402; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA232300402

gnomAD: absent

Variant 2: c.3197_3201del - unregistered variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Case: n.a.

DiseaseAssertion: VWD 2N

FamilyInfo: n.a.

ParentalGenotype(s):n.a.

CasePresentingHPOs:n.a.

CaseHPOFreeRext:n.a.

CaseNOTHPOs:n.a.

CaseNOTHPOFreeText:n.a.

CasePreviousTesting:n.a.

GenotypingMethod:n.a.

PreviouslyPublished: If applicable.n.a.

Gene:VWF

Variant:NM_000552.5(VWF):c.2278C>T (p.Arg760Cys)

HGVS:NM_000552.5:c.2278C>T

ClinVarID:100208

CAID:n.a.

gnomAD:n.a.

Gene:VWF

HGNCID:12726

Case:13 yo female

DiseaseAssertion: Type 2N

FamilyInfo:Fig. 1, family 2, patient 7

ParentalGenotype(s):Unknown, obligate carriers

CasePresentingHPOs:HP:0000421, HP:0004846, HP:0012147 HP:0030132, HP:0030130

CaseHPOFreeRext:Oral cavity and joint bleeding, VWF:Ag 0.07 U/mL, VWF:Ac 0 U/mL, VWF:CB 0.05 U/mL, FVIII 0.04 U/mL, No VWF Multimers

GenotypingMethod: NGS

Gene:VWF

Variant:c.2311A>G

HGVS:NM_000552.5(VWF):c.2311A>G

ClinVarID:1065273

CAID:CA383522481

Gene:VWF

HGNCID:12726

Case:27 yo male

DiseaseAssertion: Type 2N

FamilyInfo:Fig. 1, family 1, patient 2

ParentalGenotype(s):Unknown, obligate carriers

CasePresentingHPOs:HP:0000421, HP:0012147 HP:0030132, HP:0030130

CaseHPOFreeRext:Skin, oral cavity, and joint bleeding, Bleeding after tooth extractions and small wounds, VWF: Ag 0.07 U/mL, VWF:Act 0.05 U/mL, VWF:CB <0.05 U/mL, FVIII:C 0.01 U/mL, Less VWF Multimers

GenotypingMethod: NGS

Gene:VWF

Variant:c.2311A>G

HGVS:NM_000552.5(VWF):c.2311A>G

ClinVarID:1065273

CAID:CA383522481

Gene:VWF

HGNCID:12726

Case:17 yo male

DiseaseAssertion: Type 2N

FamilyInfo:Fig. 1, family 1, patient 3

ParentalGenotype(s):Unknown, obligate carriers

CasePresentingHPOs:HP:0000421, HP:0012147 HP:0030132, HP:0030130

CaseHPOFreeRext:Oral cavity, skin, and muscle bleeding, Bleeding after tooth extractions, VWF: Ag 0.09 U/mL, VWF:Act 0.05 U/mL, VWF:CB 0.04 U/mL, FVIII:C 0.01 U/mL, No VWF Multimers

GenotypingMethod: NGS

Gene:VWF

Variant:c.2311A>G

HGVS:NM_000552.5(VWF):c.2311A>G

ClinVarID:1065273

CAID:CA383522481