NM_000251.3(MSH2):c.1840G>T (p.Gly614Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 20, 2022
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:: RCV002560014.3

Allele description [Variation Report for NM_000251.3(MSH2):c.1840G>T (p.Gly614Ter)]

NM_000251.3(MSH2):c.1840G>T (p.Gly614Ter)

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.1840G>T (p.Gly614Ter)

HGVS:

NC_000002.12:g.47475105G>T
NG_007110.2:g.76982G>T
NM_000251.3:c.1840G>TMANE SELECT
NM_001258281.1:c.1642G>T
NP_000242.1:p.Gly614Ter
NP_001245210.1:p.Gly548Ter
LRG_218t1:c.1840G>T
LRG_218:g.76982G>T
NC_000002.11:g.47702244G>T
NC_000002.11:g.47702244G>T
NM_000251.1:c.1840G>T
NM_000251.2:c.1840G>T

Protein change:

G548*

Links:

dbSNP: rs1380847972

NCBI 1000 Genomes Browser:

rs1380847972

Molecular consequence:

NM_000251.3:c.1840G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258281.1:c.1642G>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
SCV002966438	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 20, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30693488, 15849733, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002966438

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 20, 2022)

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

Lynch-like syndrome is as frequent as Lynch syndrome in early-onset nonfamilial nonpolyposis colorectal cancer.

Antelo M, Golubicki M, Roca E, Mendez G, Carballido M, Iseas S, Cuatrecasas M, Moreira L, Sanchez A, Carballal S, Castells A, Boland CR, Goel A, Balaguer F.

Int J Cancer. 2019 Aug 1;145(3):705-713. doi: 10.1002/ijc.32160. Epub 2019 Feb 23.

PubMed [citation]

PMID:: 30693488
PMCID:: PMC10423080

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002966438.2

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 925991). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 30693488). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly614*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).

#	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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