NM_000251.3(MSH2):c.2458+4T>C AND not specified

Clinical significance:Uncertain significance (Last evaluated: Oct 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000431124.3

Allele description [Variation Report for NM_000251.3(MSH2):c.2458+4T>C]

NM_000251.3(MSH2):c.2458+4T>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.2458+4T>C
HGVS:
  • NC_000002.12:g.47478523T>C
  • NG_007110.2:g.80400T>C
  • NM_000251.3:c.2458+4T>CMANE SELECT
  • NM_001258281.1:c.2260+4T>C
  • LRG_218t1:c.2458+4T>C
  • LRG_218:g.80400T>C
  • NC_000002.11:g.47705662T>C
  • NM_000251.1:c.2458+4T>C
  • NM_000251.2:c.2458+4T>C
Links:
dbSNP: rs1038735071
NCBI 1000 Genomes Browser:
rs1038735071
Molecular consequence:
  • NM_000251.3:c.2458+4T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001258281.1:c.2260+4T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001442772Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Oct 30, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001442772.1

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

Description

Variant summary: MSH2 c.2458+4T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251202 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2458+4T>C in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as VUS (3x) or likely benign (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Nov 27, 2021

Support Center