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NM_000251.3(MSH2):c.2635-12C>G AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 23, 2024
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:
RCV002441118.3

Allele description [Variation Report for NM_000251.3(MSH2):c.2635-12C>G]

NM_000251.3(MSH2):c.2635-12C>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.2635-12C>G
HGVS:
  • NC_000002.12:g.47482767C>G
  • NG_007110.2:g.84644C>G
  • NM_000251.3:c.2635-12C>GMANE SELECT
  • NM_001258281.1:c.2437-12C>G
  • LRG_218:g.84644C>G
  • NC_000002.11:g.47709906C>G
  • NM_000251.1:c.2635-12C>G
Links:
dbSNP: rs1436357692
NCBI 1000 Genomes Browser:
rs1436357692
Molecular consequence:
  • NM_000251.3:c.2635-12C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001258281.1:c.2437-12C>G - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002744750Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jan 23, 2024) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV002744750.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.2635-12C>G intronic variant results from a C to G substitution 12 nucleotides upstream from coding exon 16 in the MSH2 gene. This variant has been identified in at least one proband who met Amsterdam I/II criteria for Lynch syndrome and tumor demonstrated loss of MSH2 and MSH6 expression by immunohistochemistry (Ambry internal data). In addition, this variant has been identified in multiple probands whose Lynch syndrome-associated tumor demonstrated high microsatellite instability and/or loss of MSH2/MSH6 expression by immunohistochemistry (Ambry internal data). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024