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NM_000251.3(MSH2):c.2334C>A (p.Cys778Ter) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 21, 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:
RCV001388594.5

Allele description [Variation Report for NM_000251.3(MSH2):c.2334C>A (p.Cys778Ter)]

NM_000251.3(MSH2):c.2334C>A (p.Cys778Ter)

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.2334C>A (p.Cys778Ter)
Other names:
p.C778*:TGC>TGA
HGVS:
  • NC_000002.12:g.47478395C>A
  • NG_007110.2:g.80272C>A
  • NM_000251.3:c.2334C>AMANE SELECT
  • NM_001258281.1:c.2136C>A
  • NP_000242.1:p.Cys778Ter
  • NP_000242.1:p.Cys778Ter
  • NP_001245210.1:p.Cys712Ter
  • LRG_218t1:c.2334C>A
  • LRG_218:g.80272C>A
  • LRG_218p1:p.Cys778Ter
  • NC_000002.11:g.47705534C>A
  • NM_000251.1:c.2334C>A
  • NM_000251.2:c.2334C>A
  • p.Cys778Stop
Protein change:
C712*
Links:
dbSNP: rs63750618
NCBI 1000 Genomes Browser:
rs63750618
Molecular consequence:
  • NM_000251.3:c.2334C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258281.1:c.2136C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001589648Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 21, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hereditary nonpolyposis colorectal cancer: an approach to the selection of candidates to genetic testing based on clinical and molecular characteristics.

Viel A, Genuardi M, Lucci-Cordisco E, Capozzi E, Rovella V, Fornasarig M, Ponz de Leòn M, Anti M, Pedroni M, Bellacosa A, Percesepe A, Covino M, Benatti P, Del Tin L, Roncucci L, Valentini M, Boiocchi M, Neri G.

Community Genet. 1998;1(4):229-36.

PubMed [citation]
PMID:
15178966

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2. doi: 10.1038/gim.2016.21.

PubMed [citation]
PMID:
26681312
PMCID:
PMC4985612
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001589648.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 90956). This premature translational stop signal has been observed in individual(s) with bladder, colon, and prostrate cancer and Lynch syndrome (LS) (PMID: 15178966, 26681312). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys778*) 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024