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NM_000251.3(MSH2):c.211+2T>C AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 15, 2022
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:
RCV000458501.6

Allele description [Variation Report for NM_000251.3(MSH2):c.211+2T>C]

NM_000251.3(MSH2):c.211+2T>C

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.211+2T>C
HGVS:
  • NC_000002.12:g.47403404T>C
  • NG_007110.2:g.5281T>C
  • NG_095167.1:g.608T>C
  • NM_000251.3:c.211+2T>CMANE SELECT
  • NM_001258281.1:c.13+2T>C
  • NM_001406631.1:c.211+2T>C
  • NM_001406632.1:c.211+2T>C
  • NM_001406633.1:c.211+2T>C
  • NM_001406634.1:c.211+2T>C
  • NM_001406635.1:c.211+2T>C
  • NM_001406636.1:c.211+2T>C
  • NM_001406637.1:c.211+2T>C
  • NM_001406638.1:c.211+2T>C
  • NM_001406639.1:c.211+2T>C
  • NM_001406640.1:c.211+2T>C
  • NM_001406641.1:c.211+2T>C
  • NM_001406642.1:c.211+2T>C
  • NM_001406643.1:c.211+2T>C
  • NM_001406644.1:c.211+2T>C
  • NM_001406645.1:c.211+2T>C
  • NM_001406646.1:c.211+2T>C
  • NM_001406647.1:c.211+2T>C
  • NM_001406648.1:c.211+2T>C
  • NM_001406649.1:c.211+2T>C
  • NM_001406650.1:c.211+2T>C
  • NM_001406651.1:c.211+2T>C
  • NM_001406652.1:c.211+2T>C
  • NM_001406653.1:c.211+2T>C
  • NM_001406654.1:c.-130+2T>C
  • NM_001406655.1:c.211+2T>C
  • NM_001406656.1:c.-785+2T>C
  • NM_001406657.1:c.211+2T>C
  • NM_001406658.1:c.-1108+2T>C
  • NM_001406659.1:c.-1258+2T>C
  • NM_001406660.1:c.-1455+2T>C
  • NM_001406661.1:c.-1410+2T>C
  • NM_001406662.1:c.-1327+2T>C
  • NM_001406666.1:c.211+2T>C
  • NM_001406669.1:c.-1258+2T>C
  • NM_001406672.1:c.211+2T>C
  • NM_001406674.1:c.211+2T>C
  • LRG_218t1:c.211+2T>C
  • LRG_218:g.5281T>C
  • NC_000002.11:g.47630543T>C
  • NM_000251.2:c.211+2T>C
Links:
dbSNP: rs1060501993
NCBI 1000 Genomes Browser:
rs1060501993
Molecular consequence:
  • NM_000251.3:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258281.1:c.13+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406631.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406632.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406633.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406634.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406635.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406636.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406637.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406638.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406639.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406640.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406641.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406642.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406643.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406644.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406645.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406646.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406647.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406648.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406649.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406650.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406651.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406652.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406653.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406654.1:c.-130+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406655.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406656.1:c.-785+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406657.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406658.1:c.-1108+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406659.1:c.-1258+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406660.1:c.-1455+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406661.1:c.-1410+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406662.1:c.-1327+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406666.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406669.1:c.-1258+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406672.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406674.1:c.211+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000548150Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 15, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Determination of splice-site mutations in Lynch syndrome (hereditary non-polyposis colorectal cancer) patients using functional splicing assay.

Naruse H, Ikawa N, Yamaguchi K, Nakamura Y, Arai M, Ishioka C, Sugano K, Tamura K, Tomita N, Matsubara N, Yoshida T, Moriya Y, Furukawa Y.

Fam Cancer. 2009;8(4):509-17. doi: 10.1007/s10689-009-9280-6. Epub 2009 Aug 15.

PubMed [citation]
PMID:
19685281

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000548150.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 19685281). ClinVar contains an entry for this variant (Variation ID: 408465). Disruption of this splice site has been observed in individual(s) with colon cancer (PMID: 19685281). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 1 of the MSH2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).

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

Last Updated: Sep 29, 2024