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NM_000251.3(MSH2):c.1986G>T (p.Gln662His) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 23, 2021
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:
RCV001882708.4

Allele description [Variation Report for NM_000251.3(MSH2):c.1986G>T (p.Gln662His)]

NM_000251.3(MSH2):c.1986G>T (p.Gln662His)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.1986G>T (p.Gln662His)
HGVS:
  • NC_000002.12:g.47475251G>T
  • NG_007110.2:g.77128G>T
  • NM_000251.3:c.1986G>TMANE SELECT
  • NM_001258281.1:c.1788G>T
  • NP_000242.1:p.Gln662His
  • NP_001245210.1:p.Gln596His
  • LRG_218t1:c.1986G>T
  • LRG_218:g.77128G>T
  • NC_000002.11:g.47702390G>T
  • NM_000251.2:c.1986G>T
Protein change:
Q596H
Links:
dbSNP: rs587780685
NCBI 1000 Genomes Browser:
rs587780685
Molecular consequence:
  • NM_000251.3:c.1986G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.1788G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002188877Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 23, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive screening for mutations associated with colorectal cancer in unselected cases reveals penetrant and nonpenetrant mutations.

Kraus C, Rau TT, Lux P, Erlenbach-Wünsch K, Löhr S, Krumbiegel M, Thiel CT, Stöhr R, Agaimy A, Croner RS, Stürzl M, Hohenberger W, Hartmann A, Reis A.

Int J Cancer. 2015 Mar 15;136(6):E559-68. doi: 10.1002/ijc.29149. Epub 2014 Aug 30.

PubMed [citation]
PMID:
25142776

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002188877.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH2 protein function. This missense change has been observed in individual(s) with colorectal cancer (PMID: 25142776). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 662 of the MSH2 protein (p.Gln662His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine.

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

Last Updated: Sep 29, 2024