NM_000251.3(MSH2):c.767C>T (p.Ala256Val) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 27, 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:: RCV003759154.2

Allele description [Variation Report for NM_000251.3(MSH2):c.767C>T (p.Ala256Val)]

NM_000251.3(MSH2):c.767C>T (p.Ala256Val)

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.767C>T (p.Ala256Val)

HGVS:

NC_000002.12:g.47412535C>T
NG_007110.2:g.14412C>T
NM_000251.3:c.767C>TMANE SELECT
NM_001258281.1:c.569C>T
NM_001406631.1:c.767C>T
NM_001406632.1:c.767C>T
NM_001406633.1:c.767C>T
NM_001406634.1:c.767C>T
NM_001406635.1:c.767C>T
NM_001406636.1:c.767C>T
NM_001406637.1:c.767C>T
NM_001406638.1:c.767C>T
NM_001406639.1:c.767C>T
NM_001406640.1:c.767C>T
NM_001406641.1:c.767C>T
NM_001406642.1:c.767C>T
NM_001406643.1:c.767C>T
NM_001406644.1:c.767C>T
NM_001406645.1:c.767C>T
NM_001406646.1:c.767C>T
NM_001406647.1:c.767C>T
NM_001406648.1:c.767C>T
NM_001406649.1:c.767C>T
NM_001406650.1:c.767C>T
NM_001406651.1:c.767C>T
NM_001406652.1:c.767C>T
NM_001406653.1:c.707C>T
NM_001406654.1:c.347C>T
NM_001406655.1:c.767C>T
NM_001406656.1:c.-229C>T
NM_001406657.1:c.767C>T
NM_001406658.1:c.-552C>T
NM_001406659.1:c.-702C>T
NM_001406660.1:c.-899C>T
NM_001406661.1:c.-854C>T
NM_001406662.1:c.-771C>T
NM_001406666.1:c.767C>T
NM_001406669.1:c.-702C>T
NM_001406672.1:c.767C>T
NM_001406674.1:c.767C>T
NP_000242.1:p.Ala256Val
NP_000242.1:p.Ala256Val
NP_001245210.1:p.Ala190Val
NP_001393560.1:p.Ala256Val
NP_001393561.1:p.Ala256Val
NP_001393562.1:p.Ala256Val
NP_001393563.1:p.Ala256Val
NP_001393564.1:p.Ala256Val
NP_001393565.1:p.Ala256Val
NP_001393566.1:p.Ala256Val
NP_001393567.1:p.Ala256Val
NP_001393568.1:p.Ala256Val
NP_001393569.1:p.Ala256Val
NP_001393570.1:p.Ala256Val
NP_001393571.1:p.Ala256Val
NP_001393572.1:p.Ala256Val
NP_001393573.1:p.Ala256Val
NP_001393574.1:p.Ala256Val
NP_001393575.1:p.Ala256Val
NP_001393576.1:p.Ala256Val
NP_001393577.1:p.Ala256Val
NP_001393578.1:p.Ala256Val
NP_001393579.1:p.Ala256Val
NP_001393580.1:p.Ala256Val
NP_001393581.1:p.Ala256Val
NP_001393582.1:p.Ala236Val
NP_001393583.1:p.Ala116Val
NP_001393584.1:p.Ala256Val
NP_001393586.1:p.Ala256Val
NP_001393595.1:p.Ala256Val
NP_001393601.1:p.Ala256Val
NP_001393603.1:p.Ala256Val
LRG_218t1:c.767C>T
LRG_218:g.14412C>T
LRG_218p1:p.Ala256Val
NC_000002.11:g.47639674C>T
NM_000251.1:c.767C>T
NM_000251.2:c.767C>T
NR_176230.1:n.803C>T
NR_176231.1:n.803C>T
NR_176232.1:n.803C>T
NR_176233.1:n.795C>T
NR_176234.1:n.803C>T
NR_176235.1:n.803C>T
NR_176236.1:n.803C>T
NR_176237.1:n.803C>T
NR_176238.1:n.803C>T
NR_176239.1:n.803C>T
NR_176240.1:n.803C>T
NR_176241.1:n.803C>T
NR_176242.1:n.803C>T
NR_176243.1:n.803C>T
NR_176244.1:n.803C>T
NR_176245.1:n.803C>T
NR_176246.1:n.803C>T
NR_176247.1:n.803C>T
NR_176248.1:n.803C>T
NR_176249.1:n.803C>T
NR_176250.1:n.803C>T

Protein change:

A116V

Molecular consequence:

NM_000251.3:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.569C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406631.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406632.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406633.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406634.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406635.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406636.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406637.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406638.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406639.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406640.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406641.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406642.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406643.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406644.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406645.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406646.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406647.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406648.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406649.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406650.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406651.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406652.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406653.1:c.707C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406654.1:c.347C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406655.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406657.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406666.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406672.1:c.767C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406674.1:c.767C>T - 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
SCV004373494	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 27, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33357406, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004373494

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 27, 2023)

germline

clinical testing

PubMed (2)
[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

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

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, SCV004373494.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. 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. ClinVar contains an entry for this variant (Variation ID: 1760104). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 256 of the MSH2 protein (p.Ala256Val).

#	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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