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NM_000251.3(MSH2):c.446G>C (p.Gly149Ala) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 29, 2018
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:
RCV000819410.6

Allele description

NM_000251.3(MSH2):c.446G>C (p.Gly149Ala)

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.446G>C (p.Gly149Ala)
HGVS:
  • NC_000002.12:g.47410173G>C
  • NG_007110.2:g.12050G>C
  • NM_000251.3:c.446G>CMANE SELECT
  • NM_001258281.1:c.248G>C
  • NP_000242.1:p.Gly149Ala
  • NP_000242.1:p.Gly149Ala
  • NP_001245210.1:p.Gly83Ala
  • LRG_218t1:c.446G>C
  • LRG_218:g.12050G>C
  • LRG_218p1:p.Gly149Ala
  • NC_000002.11:g.47637312G>C
  • NM_000251.2:c.446G>C
Protein change:
G149A
Links:
dbSNP: rs587779162
NCBI 1000 Genomes Browser:
rs587779162
Molecular consequence:
  • NM_000251.3:c.446G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.248G>C - 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
SCV000960067Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 29, 2018) 		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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000960067.4

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces glycine with alanine at codon 149 of the MSH2 protein (p.Gly149Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 491827). 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