Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000251.3(MSH2):c.1489A>G (p.Ile497Val)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(5)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 14, 2020
Accession:
VCV000230562.11
Variation ID:
230562
Description:
single nucleotide variant
Help

NM_000251.3(MSH2):c.1489A>G (p.Ile497Val)

Allele ID
232589
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p21
Genomic location
2: 47463133 (GRCh38) GRCh38 UCSC
2: 47690272 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_218:g.65010A>G
LRG_218t1:c.1489A>G LRG_218p1:p.Ile497Val
NC_000002.12:g.47463133A>G
... more HGVS
Protein change
I497V, I431V
Other names
-
Canonical SPDI
NC_000002.12:47463132:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Links
ClinGen: CA028875
dbSNP: rs755501968
VarSome
Help

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 Nov 2, 2018 RCV000483517.2
Uncertain significance 1 criteria provided, single submitter Aug 14, 2020 RCV000630079.5
Uncertain significance 1 criteria provided, single submitter May 28, 2019 RCV000986672.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jun 6, 2019 RCV000219613.4
Help
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
4521 4606

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Apr 06, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000567758.5
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted MSH2 c.1489A>G at the cDNA level, p.Ile497Val (I497V) at the protein level, and results in the change of an Isoleucine to … (more)
Uncertain significance
(Nov 02, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134339.1
Submitted: (Oct 16, 2019)
Evidence details
Uncertain significance
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Lynch syndrome I
Allele origin: unknown
Mendelics
Accession: SCV001135732.1
Submitted: (Oct 22, 2019)
Evidence details
Uncertain significance
(Jun 06, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000908304.2
Submitted: (May 19, 2020)
Evidence details
Likely benign
(Feb 22, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000274152.5
Submitted: (Nov 30, 2020)
Evidence details
Comment:
In silico models in agreement (benign);Other strong data supporting benign classification
Uncertain significance
(Aug 14, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000751035.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces isoleucine with valine at codon 497 of the MSH2 protein (p.Ile497Val). The isoleucine residue is weakly conserved and there is a … (more)

Functional evidence

Help
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

Help
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 rs755501968...

Help
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 Nov 27, 2021