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NM_000251.3(MSH2):c.1276+2T>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 26, 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:
RCV000492023.2

Allele description [Variation Report for NM_000251.3(MSH2):c.1276+2T>C]

NM_000251.3(MSH2):c.1276+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.1276+2T>C
HGVS:
  • NC_000002.12:g.47429943T>C
  • NG_007110.2:g.31820T>C
  • NM_000251.3:c.1276+2T>CMANE SELECT
  • NM_001258281.1:c.1078+2T>C
  • NM_001406631.1:c.1276+2T>C
  • NM_001406632.1:c.1276+2T>C
  • NM_001406633.1:c.1276+2T>C
  • NM_001406634.1:c.1276+2T>C
  • NM_001406635.1:c.1276+2T>C
  • NM_001406636.1:c.1243+2T>C
  • NM_001406637.1:c.1276+2T>C
  • NM_001406638.1:c.1276+2T>C
  • NM_001406639.1:c.1276+2T>C
  • NM_001406640.1:c.1276+2T>C
  • NM_001406641.1:c.1276+2T>C
  • NM_001406642.1:c.1276+2T>C
  • NM_001406643.1:c.1276+2T>C
  • NM_001406644.1:c.1276+2T>C
  • NM_001406645.1:c.1276+2T>C
  • NM_001406646.1:c.1276+2T>C
  • NM_001406647.1:c.1126+2T>C
  • NM_001406648.1:c.1276+2T>C
  • NM_001406649.1:c.1126+2T>C
  • NM_001406650.1:c.1126+2T>C
  • NM_001406651.1:c.1126+2T>C
  • NM_001406652.1:c.1126+2T>C
  • NM_001406653.1:c.1216+2T>C
  • NM_001406654.1:c.856+2T>C
  • NM_001406655.1:c.1276+2T>C
  • NM_001406656.1:c.379+2T>C
  • NM_001406657.1:c.1276+2T>C
  • NM_001406658.1:c.-81+2T>C
  • NM_001406659.1:c.-81+2T>C
  • NM_001406660.1:c.-81+2T>C
  • NM_001406661.1:c.-81+2T>C
  • NM_001406662.1:c.-81+2T>C
  • NM_001406666.1:c.1276+2T>C
  • NM_001406669.1:c.-81+2T>C
  • NM_001406672.1:c.1126+2T>C
  • NM_001406674.1:c.1276+2T>C
  • LRG_218t1:c.1276+2T>C
  • LRG_218:g.31820T>C
  • NC_000002.11:g.47657082T>C
  • NM_000251.1:c.1276+2T>C
  • NM_000251.2:c.1276+2T>C
Links:
dbSNP: rs267607953
NCBI 1000 Genomes Browser:
rs267607953
Molecular consequence:
  • NM_000251.3:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258281.1:c.1078+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406631.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406632.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406633.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406634.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406635.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406636.1:c.1243+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406637.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406638.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406639.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406640.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406641.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406642.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406643.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406644.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406645.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406646.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406647.1:c.1126+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406648.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406649.1:c.1126+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406650.1:c.1126+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406651.1:c.1126+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406652.1:c.1126+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406653.1:c.1216+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406654.1:c.856+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406655.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406656.1:c.379+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406657.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406658.1:c.-81+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406659.1:c.-81+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406660.1:c.-81+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406661.1:c.-81+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406662.1:c.-81+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406666.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406669.1:c.-81+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406672.1:c.1126+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406674.1:c.1276+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
Functional consequence:
sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)
Observations:
1

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
SCV000580619Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Feb 26, 2022) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000580619.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.1276+2T>C intronic pathogenic mutation results from a T to C substitution two nucleotides after coding exon 7 in the MSH2 gene. This variant has been identified in probands who met Amsterdam I/II criteria for Lynch syndrome and had tumors that demonstrated high microsatellite instability and/or loss of MSH2/MSH6 expression by immunohistochemistry (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). 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 pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Mar 16, 2024