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NM_000553.6(WRN):c.1922T>A (p.Val641Glu) AND Werner syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 13, 2016
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:
RCV000472604.1

Allele description [Variation Report for NM_000553.6(WRN):c.1922T>A (p.Val641Glu)]

NM_000553.6(WRN):c.1922T>A (p.Val641Glu)

Gene:
WRN:WRN RecQ like helicase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8p12
Genomic location:
Preferred name:
NM_000553.6(WRN):c.1922T>A (p.Val641Glu)
HGVS:
  • NC_000008.11:g.31096791T>A
  • NG_008870.1:g.68530T>A
  • NM_000553.6:c.1922T>AMANE SELECT
  • NP_000544.2:p.Val641Glu
  • LRG_524t1:c.1922T>A
  • LRG_524:g.68530T>A
  • NC_000008.10:g.30954307T>A
  • NM_000553.4:c.1922T>A
Protein change:
V641E
Links:
dbSNP: rs1060500069
NCBI 1000 Genomes Browser:
rs1060500069
Molecular consequence:
  • NM_000553.6:c.1922T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Werner syndrome (WRN)
Synonyms:
Werner's syndrome
Identifiers:
MONDO: MONDO:0010196; MedGen: C0043119; Orphanet: 902; OMIM: 277700

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000541437Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 13, 2016) 		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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000541437.2

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

Description

This sequence change replaces valine with glutamic acid at codon 641 of the WRN protein (p.Val641Glu). The valine residue is weakly conserved and there is a moderate physicochemical difference between valine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a WRN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "C25"). In summary, this variant is a novel missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 23, 2022