NM_000251.3(MSH2):c.211G>C (p.Gly71Arg) AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Likely pathogenic (Last evaluated: Aug 19, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000251.3(MSH2):c.211G>C (p.Gly71Arg)]

NM_000251.3(MSH2):c.211G>C (p.Gly71Arg)

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.211G>C (p.Gly71Arg)
  • NC_000002.12:g.47403402G>C
  • NG_007110.2:g.5279G>C
  • NM_000251.2:c.211G>C
  • NM_000251.3:c.211G>CMANE SELECT
  • NM_001258281.1:c.13G>C
  • NP_000242.1:p.Gly71Arg
  • NP_000242.1:p.Gly71Arg
  • NP_001245210.1:p.Gly5Arg
  • LRG_218t1:c.211G>C
  • LRG_218:g.5279G>C
  • LRG_218p1:p.Gly71Arg
  • NC_000002.11:g.47630541G>C
  • NC_000002.11:g.47630541G>C
  • NM_000251.1:c.211G>C
  • p.G71R
Protein change:
dbSNP: rs587782659
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000251.2:c.211G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000251.3:c.211G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.13G>C - missense variant - [Sequence Ontology: SO:0001583]


Hereditary nonpolyposis colorectal neoplasms
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000625353Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 19, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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



Elucidating the molecular basis of MSH2-deficient tumors by combined germline and somatic analysis.

Vargas-Parra GM, González-Acosta M, Thompson BA, Gómez C, Fernández A, Dámaso E, Pons T, Morak M, Del Valle J, Iglesias S, Velasco À, Solanes A, Sanjuan X, Padilla N, de la Cruz X, Valencia A, Holinski-Feder E, Brunet J, Feliubadaló L, Lázaro C, Navarro M, Pineda M, et al.

Int J Cancer. 2017 Oct 1;141(7):1365-1380. doi: 10.1002/ijc.30820. Epub 2017 Jul 3.

PubMed [citation]

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000625353.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)


This sequence change replaces glycine with arginine at codon 71 of the MSH2 protein (p.Gly71Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. It also falls at the last nucleotide of exon 1 of the MSH2 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Lynch syndrome (PMID: 28577310) and has been observed to segregate with Lynch syndrome-associated tumors in a single family (Invitae). ClinVar contains an entry for this variant (Variation ID: 142708). 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: Benign; Align-GVGD: Class C0). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 25, 2021

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