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NM_000251.3(MSH2):c.212-2A>G AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 7, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002415565.2

Allele description [Variation Report for NM_000251.3(MSH2):c.212-2A>G]

NM_000251.3(MSH2):c.212-2A>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.212-2A>G
HGVS:
  • NC_000002.12:g.47408399A>G
  • NG_007110.2:g.10276A>G
  • NM_000251.3:c.212-2A>GMANE SELECT
  • NM_001258281.1:c.14-2A>G
  • NM_001406631.1:c.212-2A>G
  • NM_001406632.1:c.212-2A>G
  • NM_001406633.1:c.212-2A>G
  • NM_001406634.1:c.212-2A>G
  • NM_001406635.1:c.212-2A>G
  • NM_001406636.1:c.212-2A>G
  • NM_001406637.1:c.212-2A>G
  • NM_001406638.1:c.212-2A>G
  • NM_001406639.1:c.212-2A>G
  • NM_001406640.1:c.212-2A>G
  • NM_001406641.1:c.212-2A>G
  • NM_001406642.1:c.212-2A>G
  • NM_001406643.1:c.212-2A>G
  • NM_001406644.1:c.212-2A>G
  • NM_001406645.1:c.212-2A>G
  • NM_001406646.1:c.212-2A>G
  • NM_001406647.1:c.212-2A>G
  • NM_001406648.1:c.212-2A>G
  • NM_001406649.1:c.212-2A>G
  • NM_001406650.1:c.212-2A>G
  • NM_001406651.1:c.212-2A>G
  • NM_001406652.1:c.212-2A>G
  • NM_001406653.1:c.212-62A>G
  • NM_001406654.1:c.-129-82A>G
  • NM_001406655.1:c.212-2A>G
  • NM_001406656.1:c.-784-2A>G
  • NM_001406657.1:c.212-2A>G
  • NM_001406658.1:c.-1107-2A>G
  • NM_001406659.1:c.-1257-2A>G
  • NM_001406660.1:c.-1454-2A>G
  • NM_001406661.1:c.-1409-2A>G
  • NM_001406662.1:c.-1326-2A>G
  • NM_001406666.1:c.212-2A>G
  • NM_001406669.1:c.-1257-2A>G
  • NM_001406672.1:c.212-2A>G
  • NM_001406674.1:c.212-2A>G
  • LRG_218t1:c.212-2A>G
  • LRG_218:g.10276A>G
  • NC_000002.11:g.47635538A>G
  • NM_000251.1:c.212-2A>G
  • NM_000251.2:c.212-2A>G
Links:
dbSNP: rs267607917
NCBI 1000 Genomes Browser:
rs267607917
Molecular consequence:
  • NM_001406653.1:c.212-62A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406654.1:c.-129-82A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000251.3:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001258281.1:c.14-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406631.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406632.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406633.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406634.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406635.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406636.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406637.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406638.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406639.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406640.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406641.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406642.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406643.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406644.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406645.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406646.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406647.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406648.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406649.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406650.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406651.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406652.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406655.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406656.1:c.-784-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406657.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406658.1:c.-1107-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406659.1:c.-1257-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406660.1:c.-1454-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406661.1:c.-1409-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406662.1:c.-1326-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406666.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406669.1:c.-1257-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406672.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406674.1:c.212-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002729924Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Apr 7, 2020) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

Jóri B, Kamps R, Xanthoulea S, Delvoux B, Blok MJ, Van de Vijver KK, de Koning B, Oei FT, Tops CM, Speel EJ, Kruitwagen RF, Gomez-Garcia EB, Romano A.

Oncotarget. 2015 Dec 1;6(38):41108-22. doi: 10.18632/oncotarget.5694.

PubMed [citation]
PMID:
26517685
PMCID:
PMC4747393

Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations.

Wijnen J, Khan PM, Vasen H, van der Klift H, Mulder A, van Leeuwen-Cornelisse I, Bakker B, Losekoot M, Møller P, Fodde R.

Am J Hum Genet. 1997 Aug;61(2):329-35.

PubMed [citation]
PMID:
9311737
PMCID:
PMC1715907

Details of each submission

From Ambry Genetics, SCV002729924.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.212-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 2 in the MSH2 gene. This variant (designated aagGAG>aggGAG) was identified in a family meeting Amsterdam criteria (Wijnen J et al. Am. J. Hum. Genet. 1997 Aug;61:329-35) and in a family with early onset endometrial cancer (Jóri B et al. Oncotarget 2015 Dec;6:41108-22). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

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

Last Updated: Jun 9, 2024