NM_000251.2(MSH2):c.610G>A (p.Gly204Arg) AND Lynch syndrome

Clinical significance:Uncertain significance (Last evaluated: Jul 16, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000196378.2

Allele description [Variation Report for NM_000251.2(MSH2):c.610G>A (p.Gly204Arg)]

NM_000251.2(MSH2):c.610G>A (p.Gly204Arg)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.2(MSH2):c.610G>A (p.Gly204Arg)
Other names:
p.G204R:GGA>AGA
HGVS:
  • NC_000002.12:g.47410337G>A
  • NG_007110.2:g.12214G>A
  • NM_000251.2:c.610G>A
  • NP_000242.1:p.Gly204Arg
  • LRG_218t1:c.610G>A
  • LRG_218:g.12214G>A
  • LRG_218p1:p.Gly204Arg
  • NC_000002.11:g.47637476G>A
  • NM_000251.1:c.610G>A
Protein change:
G204R
Links:
dbSNP: rs63750574
NCBI 1000 Genomes Browser:
rs63750574
Molecular consequence:
  • NM_000251.2:c.610G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Lynch syndrome (HNPCC)
Synonyms:
Hereditary nonpolyposis colon cancer
Identifiers:
MedGen: C1333990; OMIM: PS120435

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000254426Invitaecriteria provided, single submitter
Uncertain significance
(Jul 16, 2016)
germlineclinical testing

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

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.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000254426.3

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

Description

This sequence change replaces glycine with arginine at codon 204 of the MSH2 protein (p.Gly204Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 127648). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing through the creation of a novel splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function and mRNA splicing. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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: Oct 19, 2018