NM_000251.3(MSH2):c.2210+1G>A AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Likely pathogenic (Last evaluated: Oct 22, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000251.3(MSH2):c.2210+1G>A]


MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000002.12:g.47476572G>A
  • NG_007110.2:g.78449G>A
  • NM_000251.2:c.2210+1G>A
  • NM_000251.3:c.2210+1G>AMANE SELECT
  • NM_001258281.1:c.2012+1G>A
  • LRG_218t1:c.2210+1G>A
  • LRG_218:g.78449G>A
  • NC_000002.11:g.47703711G>A
  • NM_000251.1:c.2210+1G>A
dbSNP: rs267608002
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000251.2:c.2210+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_000251.3:c.2210+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258281.1:c.2012+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]


Hereditary nonpolyposis colorectal neoplasms
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000548155Invitaecriteria provided, single submitter
Likely pathogenic
(Oct 22, 2019)
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



Clinical features and mismatch repair genes analyses of Chinese suspected hereditary non-polyposis colorectal cancer: a cost-effective screening strategy proposal.

Yan HL, Hao LQ, Jin HY, Xing QH, Xue G, Mei Q, He J, He L, Sun SH.

Cancer Sci. 2008 Apr;99(4):770-80. doi: 10.1111/j.1349-7006.2008.00737.x. Epub 2008 Feb 27.

PubMed [citation]

Two germline alterations in mismatch repair genes found in a HNPCC patient with poor family history.

Kámory E, Tanyi M, Kolacsek O, Olasz J, Tóth L, Damjanovich L, Csuka O.

Pathol Oncol Res. 2006;12(4):228-33. Epub 2006 Dec 25.

PubMed [citation]
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV000548155.6

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


This sequence change affects a donor splice site in intron 13 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 the literature in individuals with early onset colorectal cancer (PMID: 18307539, 17189986), and in families with Lynch syndrome or suspected Lynch syndrome (PMID: 24710284, 12362047). ClinVar contains an entry for this variant (Variation ID: 90921). 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 30, 2021

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