NM_000251.2(MSH2):c.2006-2A>G AND Hereditary nonpolyposis colon cancer

Clinical significance:Pathogenic (Last evaluated: May 5, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001420710.1

Allele description [Variation Report for NM_000251.2(MSH2):c.2006-2A>G]

NM_000251.2(MSH2):c.2006-2A>G

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.2(MSH2):c.2006-2A>G
HGVS:
  • NC_000002.12:g.47476365A>G
  • NG_007110.2:g.78242A>G
  • NM_000251.2:c.2006-2A>G
  • NM_001258281.1:c.1808-2A>G
  • LRG_218t1:c.2006-2A>G
  • LRG_218:g.78242A>G
  • NC_000002.11:g.47703504A>G
  • NM_000251.1:c.2006-2A>G
Links:
dbSNP: rs267607991
NCBI 1000 Genomes Browser:
rs267607991
Molecular consequence:
  • NM_000251.2:c.2006-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001258281.1:c.1808-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:
Hereditary nonpolyposis colorectal cancer
Identifiers:
MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000917706Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(May 5, 2021)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Cancer risk in 348 French MSH2 or MLH1 gene carriers.

Parc Y, Boisson C, Thomas G, Olschwang S.

J Med Genet. 2003 Mar;40(3):208-13. No abstract available.

PubMed [citation]
PMID:
12624141
PMCID:
PMC1735402

Novel germline and somatic mutations of the MSH2 gene in hereditary non-polyposis colorectal cancer.

Ding DC, Huang RL, Chen CH, Chao CF, Chu TY.

Clin Genet. 2007 Feb;71(2):190-2. No abstract available.

PubMed [citation]
PMID:
17250671
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917706.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: MSH2 c.2006-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a canonical 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing resulting in exon 13 skipping (example, Ding_2007). The variant was absent in 251336 control chromosomes. c.2006-2A>G has been reported in the literature in individuals affected with Hereditary Nonpolyposis Colorectal Cancer/Lynch syndrome (example, Ding_2007, Morak_2017, Parc_2003). These data indicate that the variant may be associated with disease. One clinical diagnostic laboratory and an expert panel (InSiGHT) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Oct 8, 2021

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