NM_000553.6(WRN):c.1920C>G (p.Tyr640Ter) AND Werner syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 4, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001390198.1

Allele description [Variation Report for NM_000553.6(WRN):c.1920C>G (p.Tyr640Ter)]

NM_000553.6(WRN):c.1920C>G (p.Tyr640Ter)

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.1920C>G (p.Tyr640Ter)
HGVS:
  • NC_000008.11:g.31096789C>G
  • NG_008870.1:g.68528C>G
  • NM_000553.6:c.1920C>GMANE SELECT
  • NP_000544.2:p.Tyr640Ter
  • LRG_524:g.68528C>G
  • NC_000008.10:g.30954305C>G
Protein change:
Y640*
Molecular consequence:
  • NM_000553.6:c.1920C>G - nonsense - [Sequence Ontology: SO:0001587]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001591835Invitaecriteria provided, single submitter
Pathogenic
(Sep 4, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The spectrum of WRN mutations in Werner syndrome patients.

Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, et al.

Hum Mutat. 2006 Jun;27(6):558-67.

PubMed [citation]
PMID:
16673358
PMCID:
PMC1868417

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, SCV001591835.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Tyr640*) in the WRN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with WRN-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in WRN are known to be pathogenic (PMID: 16673358). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

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