NM_000251.3(MSH2):c.166G>A (p.Glu56Lys) AND Lynch syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 6, 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:: RCV003997405.1

Allele description

NM_000251.3(MSH2):c.166G>A (p.Glu56Lys)

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.166G>A (p.Glu56Lys)

HGVS:

NC_000002.12:g.47403357G>A
NG_007110.2:g.5234G>A
NM_000251.3:c.166G>AMANE SELECT
NM_001258281.1:c.-30-3G>A
NP_000242.1:p.Glu56Lys
NP_000242.1:p.Glu56Lys
LRG_218t1:c.166G>A
LRG_218:g.5234G>A
LRG_218p1:p.Glu56Lys
NC_000002.11:g.47630496G>A
NM_000251.1:c.166G>A
NM_000251.2:c.166G>A

Protein change:

E56K

Links:

dbSNP: rs587779102

NCBI 1000 Genomes Browser:

rs587779102

Molecular consequence:

NM_001258281.1:c.-30-3G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000251.3:c.166G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004831950	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Oct 6, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23047549, 31997046, 33357406, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004831950

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Oct 6, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	3	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.

Pal T, Akbari MR, Sun P, Lee JH, Fulp J, Thompson Z, Coppola D, Nicosia S, Sellers TA, McLaughlin J, Risch HA, Rosen B, Shaw P, Schildkraut J, Narod SA.

Br J Cancer. 2012 Nov 6;107(10):1783-90. doi: 10.1038/bjc.2012.452. Epub 2012 Oct 9.

PubMed [citation]

PMID:: 23047549
PMCID:: PMC3493867

Detection of DNA mismatch repair deficient crypts in random colonoscopic biopsies identifies Lynch syndrome patients.

Brand RE, Dudley B, Karloski E, Das R, Fuhrer K, Pai RK, Pai RK.

Fam Cancer. 2020 Apr;19(2):169-175. doi: 10.1007/s10689-020-00161-w.

PubMed [citation]

PMID:: 31997046

See all PubMed Citations (4)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004831950.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (4)

Description

This missense variant replaces glutamic acid with lysine at codon 56 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 ovarian cancer (PMID: 23047549) and an individual affected with colon cancer (PMID: 31997046). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		3	not provided	not provided	not provided

Last Updated: May 1, 2024

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