NM_000251.3(MSH2):c.366+1G>A AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Pathogenic (Last evaluated: Jan 31, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000791394.3

Allele description [Variation Report for NM_000251.3(MSH2):c.366+1G>A]

NM_000251.3(MSH2):c.366+1G>A

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.366+1G>A
HGVS:
  • NC_000002.12:g.47408556G>A
  • NG_007110.2:g.10433G>A
  • NM_000251.3:c.366+1G>AMANE SELECT
  • NM_001258281.1:c.168+1G>A
  • LRG_218t1:c.366+1G>A
  • LRG_218:g.10433G>A
  • NC_000002.11:g.47635695G>A
  • NM_000251.1:c.366+1G>A
  • NM_000251.2:c.366+1G>A
Links:
dbSNP: rs267607924
NCBI 1000 Genomes Browser:
rs267607924
Molecular consequence:
  • NM_000251.3:c.366+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258281.1:c.168+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000548172Invitaecriteria provided, single submitter
Pathogenic
(Jan 31, 2020)
germlineclinical testing

PubMed (7)
[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

Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC).

Geary J, Sasieni P, Houlston R, Izatt L, Eeles R, Payne SJ, Fisher S, Hodgson SV.

Fam Cancer. 2008;7(2):163-72. Epub 2007 Oct 16.

PubMed [citation]
PMID:
17939062

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations.

Sjursen W, McPhillips M, Scott RJ, Talseth-Palmer BA.

Mol Genet Genomic Med. 2016 Mar;4(2):223-31. doi: 10.1002/mgg3.198.

PubMed [citation]
PMID:
27064304
PMCID:
PMC4799874
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000548172.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change affects a donor splice site in intron 2 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 observed in individuals with clinical features of Lynch syndrome (PMID: 17939062, 27064304, 25430799). Additionally, it has also been observed to segregate with disease in Lynch syndrome families (Invitae). ClinVar contains an entry for this variant (Variation ID: 245947). 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: Nov 27, 2021

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