NM_000553.6(WRN):c.1835C>G (p.Ser612Cys) AND Werner syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 16, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000552831.7

Allele description [Variation Report for NM_000553.6(WRN):c.1835C>G (p.Ser612Cys)]

NM_000553.6(WRN):c.1835C>G (p.Ser612Cys)

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.1835C>G (p.Ser612Cys)
HGVS:
  • NC_000008.11:g.31091835C>G
  • NG_008870.1:g.63574C>G
  • NM_000553.6:c.1835C>GMANE SELECT
  • NP_000544.2:p.Ser612Cys
  • LRG_524t1:c.1835C>G
  • LRG_524:g.63574C>G
  • NC_000008.10:g.30949351C>G
  • NM_000553.4:c.1835C>G
  • Q14191:p.Ser612Cys
Protein change:
S612C
Links:
UniProtKB: Q14191#VAR_018943; dbSNP: rs11574250
NCBI 1000 Genomes Browser:
rs11574250
Molecular consequence:
  • NM_000553.6:c.1835C>G - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000629625Invitaecriteria provided, single submitter
Uncertain significance
(Oct 16, 2020)
germlineclinical testing

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

SCV001320243Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

Citation Link

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, SCV000629625.6

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

Description

This sequence change replaces serine with cysteine at codon 612 of the WRN protein (p.Ser612Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs11574250, ExAC 0.2%). This variant has not been reported in the literature in individuals with WRN-related disease. ClinVar contains an entry for this variant (Variation ID: 135419). 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: Probably Damaging; Align-GVGD: Class C1). 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. 5

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

From Illumina Clinical Services Laboratory,Illumina, SCV001320243.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

Last Updated: Oct 7, 2021

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