U.S. flag

An official website of the United States government

NM_000251.3(MSH2):c.2334C>A (p.Cys778Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 13, 2021
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:
RCV000491112.4

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 cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000580388Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 13, 2021) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Evaluation of the replication error phenotype in relation to molecular and clinicopathological features in hereditary and early onset colorectal cancer.

Capozzi E, Della Puppa L, Fornasarig M, Pedroni M, Boiocchi M, Viel A.

Eur J Cancer. 1999 Feb;35(2):289-95.

PubMed [citation]
PMID:
10448273

Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer.

Ponz de Leon M, Benatti P, Di Gregorio C, Pedroni M, Losi L, Genuardi M, Viel A, Fornasarig M, Lucci-Cordisco E, Anti M, Ponti G, Borghi F, Lamberti I, Roncucci L.

Br J Cancer. 2004 Feb 23;90(4):882-7.

PubMed [citation]
PMID:
14970868
PMCID:
PMC2410159
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000580388.6

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

Description

The p.C778* pathogenic mutation (also known as c.2334C>A), located in coding exon 14 of the MSH2 gene, results from a C to A substitution at nucleotide position 2334. This changes the amino acid from a cysteine to a stop codon within coding exon 14. This mutation has been detected in multiple individuals and families with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome meeting Amsterdam criteria, including individuals whose tumors demonstrated high microsatellite instability (MSI-H) (Viel A et al. Community Genet, 1998;1:229-36; Capozzi E et al. Eur. J. Cancer, 1999 Feb;35:289-95; Ponz de Leon M et al. Br J Cancer, 2004 Feb;90:882-7; Pastrello C et al. Genet Med, 2011 Feb;13:115-24; Fornasarig M et al. Int J Mol Sci, 2018 06;19). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024