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NM_000251.3(MSH2):c.2551C>G (p.Leu851Val) AND Lynch syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 23, 2023
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:
RCV003997534.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2551C>G (p.Leu851Val)]

NM_000251.3(MSH2):c.2551C>G (p.Leu851Val)

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.2551C>G (p.Leu851Val)
Other names:
p.Leu851Val
HGVS:
  • NC_000002.12:g.47480788C>G
  • NG_007110.2:g.82665C>G
  • NM_000251.3:c.2551C>GMANE SELECT
  • NM_001258281.1:c.2353C>G
  • NP_000242.1:p.Leu851Val
  • NP_000242.1:p.Leu851Val
  • NP_001245210.1:p.Leu785Val
  • LRG_218t1:c.2551C>G
  • LRG_218:g.82665C>G
  • LRG_218p1:p.Leu851Val
  • NC_000002.11:g.47707927C>G
  • NM_000251.1:c.2551C>G
  • NM_000251.2:c.2551C>G
  • p.L851V
Protein change:
L785V
Links:
dbSNP: rs267608015
NCBI 1000 Genomes Browser:
rs267608015
Molecular consequence:
  • NM_000251.3:c.2551C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.2353C>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Lynch syndrome
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004826431All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Aug 23, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.

Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, Garcia RL, King MC, Swisher EM.

Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18032-7. doi: 10.1073/pnas.1115052108. Epub 2011 Oct 17.

PubMed [citation]
PMID:
22006311
PMCID:
PMC3207658

Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.

Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO.

Am J Hum Genet. 2021 Jan 7;108(1):163-175. doi: 10.1016/j.ajhg.2020.12.003. Epub 2020 Dec 23.

PubMed [citation]
PMID:
33357406
PMCID:
PMC7820803
See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004826431.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces leucine with valine at codon 851 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with colorectal cancer who had two or more family members affected with Lynch syndrome-associated cancers (PMID 18726168), as well as in an individual affected with ovarian, peritoneal, or fallopian tube carcinoma (PMID: 22006311). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024