NM_000251.3(MSH2):c.1662-2A>G AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Pathogenic (Last evaluated: Feb 4, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000560516.3

Allele description [Variation Report for NM_000251.3(MSH2):c.1662-2A>G]

NM_000251.3(MSH2):c.1662-2A>G

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.1662-2A>G
HGVS:
  • NC_000002.12:g.47470963A>G
  • NG_007110.2:g.72840A>G
  • NM_000251.2:c.1662-2A>G
  • NM_000251.3:c.1662-2A>GMANE SELECT
  • NM_001258281.1:c.1464-2A>G
  • LRG_218t1:c.1662-2A>G
  • LRG_218:g.72840A>G
  • NC_000002.11:g.47698102A>G
  • NC_000002.11:g.47698102A>G
  • NM_000251.1:c.1662-2A>G
Links:
dbSNP: rs267607971
NCBI 1000 Genomes Browser:
rs267607971
Molecular consequence:
  • NM_000251.2:c.1662-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_000251.3:c.1662-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001258281.1:c.1464-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000625295Invitaecriteria provided, single submitter
Pathogenic
(Feb 4, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families.

Wang XL, Yuan Y, Zhang SZ, Cai SR, Huang YQ, Jiang Q, Zheng S.

World J Gastroenterol. 2006 Jul 7;12(25):4074-7.

PubMed [citation]
PMID:
16810763
PMCID:
PMC4087725

Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.

Bonadona V, Bonaïti B, Olschwang S, Grandjouan S, Huiart L, Longy M, Guimbaud R, Buecher B, Bignon YJ, Caron O, Colas C, Noguès C, Lejeune-Dumoulin S, Olivier-Faivre L, Polycarpe-Osaer F, Nguyen TD, Desseigne F, Saurin JC, Berthet P, Leroux D, Duffour J, Manouvrier S, et al.

JAMA. 2011 Jun 8;305(22):2304-10. doi: 10.1001/jama.2011.743.

PubMed [citation]
PMID:
21642682
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000625295.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change affects an acceptor splice site in intron 10 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in families affected with Lynch syndrome (PMID: 16810763, 21642682). ClinVar contains an entry for this variant (Variation ID: 90728). A different variant affecting this nucleotide (c.1662-2A>C) has been determined to be pathogenic (PMID: 18566915, 24090359). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 25, 2021

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