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.2006-1G>C

Help
Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Jun 21, 2019
Accession:
VCV000090845.5
Variation ID:
90845
Description:
single nucleotide variant
Help

NM_000251.3(MSH2):c.2006-1G>C

Allele ID
96320
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p21
Genomic location
2: 47476366 (GRCh38) GRCh38 UCSC
2: 47703505 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.47703505G>C
NM_000251.2:c.2006-1G>C splice acceptor
LRG_218:g.78243G>C
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000002.12:47476365:G:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA019741
dbSNP: rs267607988
VarSome
Help

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 RCV000076347.3
Pathogenic 1 criteria provided, single submitter Feb 27, 2020 RCV000491159.2
Likely pathogenic 1 criteria provided, single submitter Feb 9, 2020 RCV001379378.1
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
Likely pathogenic
(Jun 21, 2019)
reviewed by expert panel
Method: curation
Lynch syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107373.3
Submitted: (Jun 21, 2019)
Evidence details
Other databases
http://www.insight-database.org/…
Comment:
Interrupts canonical donor splice site
Pathogenic
(Feb 27, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000580477.4
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (5)
Comment:
The c.2006-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 13 of the MSH2 gene. This mutation … (more)
Likely pathogenic
(Feb 09, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV001577172.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change affects an acceptor splice site in intron 12 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results … (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
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
Lynch syndrome in Tunisia: first description of clinical features and germline mutations. Moussa SA International journal of colorectal disease 2011 PMID: 21311894
Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers. Sjursen W Journal of medical genetics 2010 PMID: 20587412
Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectal cancers. Nagasaka T Cancer research 2010 PMID: 20388775
Splicing in action: assessing disease causing sequence changes. Baralle D Journal of medical genetics 2005 PMID: 16199547
Immunohistochemistry identifies carriers of mismatch repair gene defects causing hereditary nonpolyposis colorectal cancer. Stormorken AT Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005 PMID: 16034045
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
http://www.insight-database.org/classifications/?gene=MSH2&variant=c.2006-1G%3EC - - - -

Text-mined citations for rs267607988...

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