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NM_000553.6(WRN):c.445C>T (p.Arg149Cys) AND Werner syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 18, 2023
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:
RCV000633187.5

Allele description [Variation Report for NM_000553.6(WRN):c.445C>T (p.Arg149Cys)]

NM_000553.6(WRN):c.445C>T (p.Arg149Cys)

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.445C>T (p.Arg149Cys)
HGVS:
  • NC_000008.11:g.31065004C>T
  • NG_008870.1:g.36743C>T
  • NM_000553.6:c.445C>TMANE SELECT
  • NP_000544.2:p.Arg149Cys
  • LRG_524t1:c.445C>T
  • LRG_524:g.36743C>T
  • NC_000008.10:g.30922520C>T
  • NM_000553.4:c.445C>T
Protein change:
R149C
Links:
dbSNP: rs752693894
NCBI 1000 Genomes Browser:
rs752693894
Molecular consequence:
  • NM_000553.6:c.445C>T - 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
SCV000754402Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 18, 2023) 		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, SCV000754402.5

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 149 of the WRN protein (p.Arg149Cys). This variant is present in population databases (rs752693894, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 528104). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. 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: Feb 20, 2024