NM_000251.3(MSH2):c.2047G>A (p.Gly683Arg) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 7, 2024
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:: RCV000524373.9

Allele description [Variation Report for NM_000251.3(MSH2):c.2047G>A (p.Gly683Arg)]

NM_000251.3(MSH2):c.2047G>A (p.Gly683Arg)

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.2047G>A (p.Gly683Arg)

HGVS:

NC_000002.12:g.47476408G>A
NG_007110.2:g.78285G>A
NM_000251.3:c.2047G>AMANE SELECT
NM_001258281.1:c.1849G>A
NP_000242.1:p.Gly683Arg
NP_000242.1:p.Gly683Arg
NP_001245210.1:p.Gly617Arg
LRG_218t1:c.2047G>A
LRG_218:g.78285G>A
LRG_218p1:p.Gly683Arg
NC_000002.11:g.47703547G>A
NM_000251.1:c.2047G>A
NM_000251.2:c.2047G>A
p.G683R

Protein change:

G617R

Links:

dbSNP: rs267607995

NCBI 1000 Genomes Browser:

rs267607995

Molecular consequence:

NM_000251.3:c.2047G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.1849G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000253804	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 7, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11606497, 18931482, 19731080, 26248088, 33357406, 23690608, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000253804

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 7, 2024)

germline

clinical testing

PubMed (7)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer.

Samowitz WS, Curtin K, Lin HH, Robertson MA, Schaffer D, Nichols M, Gruenthal K, Leppert MF, Slattery ML.

Gastroenterology. 2001 Oct;121(4):830-8.

PubMed [citation]

PMID:: 11606497

Mismatch repair gene mutations in Chinese HNPCC patients.

Sheng JQ, Fu L, Sun ZQ, Huang JS, Han M, Mu H, Zhang H, Zhang YZ, Zhang MZ, Li AQ, Wu ZT, Han Y, Li SR.

Cytogenet Genome Res. 2008;122(1):22-7. doi: 10.1159/000151312. Epub 2008 Oct 14.

PubMed [citation]

PMID:: 18931482

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000253804.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 683 of the MSH2 protein (p.Gly683Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of MSH2-related conditions (PMID: 11606497, 18931482, 19731080, 26248088; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 90868). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is expected to disrupt MSH2 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects MSH2 function (PMID: 23690608). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024

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