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NM_000251.3(MSH2):c.943-1G>C

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel
Submissions:
5 (Most recent: Oct 27, 2021)
Last evaluated:
Jun 21, 2019
Accession:
VCV000091253.8
Variation ID:
91253
Description:
single nucleotide variant
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NM_000251.3(MSH2):c.943-1G>C

Allele ID
96728
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p21
Genomic location
2: 47643434 (GRCh37) GRCh37 UCSC
2: 47416295 (GRCh38) GRCh38 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_218:g.18172G>C
LRG_218t1:c.943-1G>C
NC_000002.11:g.47643434G>C
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000002.12:47416294:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA022602
dbSNP: rs12476364
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 reviewed by expert panel Jun 21, 2019 RCV000076758.4
Pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 20, 2021 RCV001531920.2
Pathogenic 1 criteria provided, single submitter Nov 28, 2017 RCV000491758.2
Pathogenic 1 criteria provided, single submitter Feb 29, 2020 RCV000696831.3
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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
4521 4606

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Jun 21, 2019)
reviewed by expert panel
Method: curation
Lynch syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107799.3
Submitted: (Jun 21, 2019)
Evidence details
Other databases
http://www.insight-database.org/…
Comment:
Interrupts canonical donor splice site
Pathogenic
(Nov 28, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000580427.4
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.943-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 6 of the MSH2 gene. This variant … (more)
Pathogenic
(Feb 29, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000825410.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change affects an acceptor splice site in intron 5 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results … (more)
Pathogenic
(Jun 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001747251.1
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(Oct 20, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001983801.1
Submitted: (Oct 27, 2021)
Evidence details
Comment:
Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed … (more)

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
A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America. Rossi BM BMC cancer 2017 PMID: 28874130
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
Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Thompson BA Nature genetics 2014 PMID: 24362816
Splicing in action: assessing disease causing sequence changes. Baralle D Journal of medical genetics 2005 PMID: 16199547
Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer. Mangold E International journal of cancer 2005 PMID: 15849733
Clinical consequences of molecular diagnosis in families with mismatch repair gene germline mutations. Pistorius SR International journal of colorectal disease 2000 PMID: 11151427
http://www.insight-database.org/classifications/?gene=MSH2&variant=c.943-1G%3EC - - - -

Text-mined citations for rs12476364...

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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 Nov 27, 2021