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NM_000552.5(VWF):c.2561G>A (p.Arg854Gln) AND VWF-related condition

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 2, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003415598.5

Allele description

NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)

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.2561G>A (p.Arg854Gln)
Other names:
p.R854Q
HGVS:
  • NC_000012.12:g.6034812C>T
  • NG_009072.2:g.94859G>A
  • NM_000552.5:c.2561G>AMANE SELECT
  • NM_000552.5:c.2561G>A
  • NP_000543.2:p.Arg854Gln
  • NP_000543.3:p.Arg854Gln
  • LRG_587t1:c.2561G>A
  • LRG_587:g.94859G>A
  • LRG_587p1:p.Arg854Gln
  • NC_000012.11:g.6143978C>T
  • NC_000012.12:g.6034812C>T
  • NG_009072.1:g.94859G>A
  • NM_000552.2:c.2561G>A
  • NM_000552.3:c.2561G>A
  • NM_000552.4:c.2561G>A
  • P04275:p.Arg854Gln
Protein change:
R854Q; ARG854GLN
Links:
UniProtKB: P04275#VAR_005789; OMIM: 613160.0013; dbSNP: rs41276738
NCBI 1000 Genomes Browser:
rs41276738
Molecular consequence:
  • NM_000552.5:c.2561G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
VWF-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004117618PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 2, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004117618.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The VWF c.2561G>A variant is predicted to result in the amino acid substitution p.Arg854Gln. This variant (aka p.Arg91Gln) has been reported in the homozygous or compound heterozygous state in many patients with recessive von Willebrand disease (VWD) type 2N (van Meergeren et al. 2015. PubMed ID: 26207643; Castaman et al. 2010. PubMed ID: 20586924; Gaucher et al. 1991. PubMed ID: 1832934; Hilbert et al. 2004. PubMed ID: 15461624). One patient with VWD type 1 was also reported to have the p.Arg854Gln substitution (Peerlinck et al. 1992. PubMed ID: 1581215). Different cellular and biochemical studies indicate the p.Arg854Gln change alters normal VWF protein function (Cacheris et al. 1991. PubMed ID: 1906877; Castaman et al. 2010. PubMed ID: 20586924; Wang et al. 2013. PubMed ID: 23426949; Hilbert et al. 2004. PubMed ID: 15461624). This variant is reported in 0.57% of alleles in individuals of European (Finnish) descent in gnomAD, including several homozygotes. Multiple laboratories classify this variant as pathogenic or likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/296/). This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024