NM_000251.3(MSH2):c.478C>T (p.Gln160Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 5, 2020
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:: RCV000547313.6

Allele description [Variation Report for NM_000251.3(MSH2):c.478C>T (p.Gln160Ter)]

NM_000251.3(MSH2):c.478C>T (p.Gln160Ter)

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.478C>T (p.Gln160Ter)

HGVS:

NC_000002.12:g.47410205C>T
NG_007110.2:g.12082C>T
NM_000251.3:c.478C>TMANE SELECT
NM_001258281.1:c.280C>T
NP_000242.1:p.Gln160Ter
NP_000242.1:p.Gln160Ter
NP_001245210.1:p.Gln94Ter
LRG_218t1:c.478C>T
LRG_218:g.12082C>T
LRG_218p1:p.Gln160Ter
NC_000002.11:g.47637344C>T
NM_000251.1:c.478C>T
NM_000251.2:c.478C>T

Protein change:

Q160*

Links:

dbSNP: rs63751426

NCBI 1000 Genomes Browser:

rs63751426

Molecular consequence:

NM_000251.3:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.280C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000625429	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 5, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15849733, 24362816, 15235030, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000625429

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 5, 2020)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer.

Mangold E, Pagenstecher C, Friedl W, Mathiak M, Buettner R, Engel C, Loeffler M, Holinski-Feder E, Müller-Koch Y, Keller G, Schackert HK, Krüger S, Goecke T, Moeslein G, Kloor M, Gebert J, Kunstmann E, Schulmann K, Rüschoff J, Propping P.

Int J Cancer. 2005 Sep 20;116(5):692-702.

PubMed [citation]

PMID:: 15849733

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]

PMID:: 24362816
PMCID:: PMC4294709

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000625429.4

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been reported in an individual affected with Muir-Torre syndrome (PMID: 15235030). ClinVar contains an entry for this variant (Variation ID: 91103). This sequence change creates a premature translational stop signal (p.Gln160*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product.

#	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: May 7, 2024

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