NM_000552.5(VWF):c.1922C>T (p.Ala641Val) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 31, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004595919.2

Allele description [Variation Report for NM_000552.5(VWF):c.1922C>T (p.Ala641Val)]

NM_000552.5(VWF):c.1922C>T (p.Ala641Val)

Gene:

VWF:von Willebrand factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.31

Genomic location:

Preferred name:

NM_000552.5(VWF):c.1922C>T (p.Ala641Val)

HGVS:

NC_000012.12:g.6056880G>A
NG_009072.2:g.72791C>T
NM_000552.4:c.1922C>T
NM_000552.5:c.1922C>TMANE SELECT
NP_000543.3:p.Ala641Val
LRG_587t1:c.1922C>T
LRG_587:g.72791C>T
LRG_587p1:p.Ala641Val
NC_000012.11:g.6166046G>A
NG_009072.1:g.72791C>T
NM_000552.2:c.1922C>T
NM_000552.3:c.1922C>T
NM_000552.5:c.1922C>T

Protein change:

A641V

Links:

dbSNP: rs61754019

NCBI 1000 Genomes Browser:

rs61754019

Molecular consequence:

NM_000552.5:c.1922C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005090408	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005185282	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 9, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16985174, 31064749, 33556167 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005090408

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 31, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005185282

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 9, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD).

Goodeve A, Eikenboom J, Castaman G, Rodeghiero F, Federici AB, Batlle J, Meyer D, Mazurier C, Goudemand J, Schneppenheim R, Budde U, Ingerslev J, Habart D, Vorlova Z, Holmberg L, Lethagen S, Pasi J, Hill F, Hashemi Soteh M, Baronciani L, Hallden C, Guilliatt A, et al.

Blood. 2007 Jan 1;109(1):112-21. Epub 2006 Sep 19. Erratum in: Blood. 2008 Mar 15;111(6):3299-300.

PubMed [citation]

PMID:: 16985174

See all PubMed Citations (4)

Details of each submission

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV005090408.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005185282.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: VWF c.1922C>T (p.Ala641Val) results in a non-conservative amino acid change located in the VWF/SSPO/Zonadhesin-like, cysteine-rich domain (IPR014853) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 84122 control chromosomes. c.1922C>T has been reported in the literature in individuals affected with Von Willebrand Disease (example, Downes_2019, Goodeve_2007, Sadler_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Von Willebrand Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31064749, 16985174, 33556167). ClinVar contains an entry for this variant (Variation ID: 100196). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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