NM_000251.3(MSH2):c.2006-1G>C AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Likely pathogenic (Last evaluated: Feb 9, 2020)

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.2006-1G>C]


MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000002.12:g.47476366G>C
  • NG_007110.2:g.78243G>C
  • NM_000251.3:c.2006-1G>CMANE SELECT
  • NM_001258281.1:c.1808-1G>C
  • LRG_218t1:c.2006-1G>C
  • LRG_218:g.78243G>C
  • NC_000002.11:g.47703505G>C
  • NM_000251.1:c.2006-1G>C
  • NM_000251.2:c.2006-1G>C
dbSNP: rs267607988
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000251.3:c.2006-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001258281.1:c.1808-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]


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)
SCV001577172Invitaecriteria provided, single submitter
Likely pathogenic
(Feb 9, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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



Immunohistochemistry identifies carriers of mismatch repair gene defects causing hereditary nonpolyposis colorectal cancer.

Stormorken AT, Bowitz-Lothe IM, Norèn T, Kure E, Aase S, Wijnen J, Apold J, Heimdal K, Møller P.

J Clin Oncol. 2005 Jul 20;23(21):4705-12.

PubMed [citation]

Lynch syndrome in Tunisia: first description of clinical features and germline mutations.

Moussa SA, Moussa A, Kourda N, Mezlini A, Abdelli N, Zerimech F, Najjar T, Jilani SB, Porchet N, Ayed FB, Manai M, Buisine MP.

Int J Colorectal Dis. 2011 Apr;26(4):455-67. doi: 10.1007/s00384-010-1129-9. Epub 2011 Feb 11.

PubMed [citation]
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001577172.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)


This sequence change affects an acceptor splice site in intron 12 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 individual(s) with Lynch syndrome (PMID: 15849733, 16034045, 21311894). This variant is also known as IVS12-1G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 90845). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Dec 4, 2021

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