NM_000553.6(WRN):c.3493C>T (p.Gln1165Ter) AND Werner syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 19, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000005778.5

Allele description [Variation Report for NM_000553.6(WRN):c.3493C>T (p.Gln1165Ter)]

NM_000553.6(WRN):c.3493C>T (p.Gln1165Ter)

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.3493C>T (p.Gln1165Ter)
HGVS:
  • NC_000008.11:g.31147397C>T
  • NG_008870.1:g.119136C>T
  • NM_000553.6:c.3493C>TMANE SELECT
  • NP_000544.2:p.Gln1165Ter
  • LRG_524t1:c.3493C>T
  • LRG_524:g.119136C>T
  • NC_000008.10:g.31004913C>T
  • NM_000553.4:c.3493C>T
Protein change:
Q1165*; GLN1165TER
Links:
OMIM: 604611.0002; dbSNP: rs121908447
NCBI 1000 Genomes Browser:
rs121908447
Molecular consequence:
  • NM_000553.6:c.3493C>T - 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
SCV000025960OMIMno assertion criteria providedPathogenic
(Apr 12, 1996)
germlineliterature only

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

SCV000934312Invitaecriteria provided, single submitter
Pathogenic
(Sep 19, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Positional cloning of the Werner's syndrome gene.

Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD.

Science. 1996 Apr 12;272(5259):258-62.

PubMed [citation]
PMID:
8602509

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 OMIM, SCV000025960.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a Japanese patient with Werner syndrome (WRN; 277700) whose parents were first cousins, Yu et al. (1996) found homozygosity for a change of codon 1165 of the WRN gene from CAG (gln) to TAG (stop) (Q1165X).

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

From Invitae, SCV000934312.1

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

Description

This sequence change creates a premature translational stop signal (p.Gln1165*) 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 been observed in individuals affected with Werner syndrome (PMID: 8602509, 8968742, 20443122). This variant is also known as c.3724C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 5445). 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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