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NM_000251.3(MSH2):c.2458+4T>C

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Sep 28, 2021)
Last evaluated:
Nov 10, 2020
Accession:
VCV000386321.9
Variation ID:
386321
Description:
single nucleotide variant
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NM_000251.3(MSH2):c.2458+4T>C

Allele ID
366728
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p21
Genomic location
2: 47478523 (GRCh38) GRCh38 UCSC
2: 47705662 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.47705662T>C
LRG_218:g.80400T>C
LRG_218t1:c.2458+4T>C
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000002.12:47478522:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA16604275
dbSNP: rs1038735071
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Oct 31, 2019 RCV000574853.2
Uncertain significance 1 criteria provided, single submitter Oct 30, 2020 RCV000431124.3
Likely benign 1 criteria provided, single submitter Nov 10, 2020 RCV000630059.5
Likely benign 1 criteria provided, single submitter Sep 12, 2019 RCV001712259.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MSH2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
4518 4603

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Apr 17, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000669797.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.2458+4T>C intronic variant results from a T to C substitution 4 nucleotides after coding exon 14 in the MSH2 gene. This nucleotide position is … (more)
Likely benign
(Sep 12, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000527911.5
Submitted: (Sep 28, 2021)
Evidence details
Uncertain significance
(Oct 31, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV001357312.1
Submitted: (May 19, 2020)
Comment:
This variant causes a T>C nucleotide substitution at the +4 position of intron 14 of the MSH2 gene. To our knowledge, functional studies have not … (more)
Evidence details
Uncertain significance
(Oct 30, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001442772.1
Submitted: (Nov 10, 2020)
Evidence details
Comment:
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 … (more)
Likely benign
(Nov 10, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000751015.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532

Text-mined citations for rs1038735071...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 30, 2021