ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.289C>T (p.Gln97Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000251.3(MSH2):c.289C>T (p.Gln97Ter)
Variation ID: 91054 Accession: VCV000091054.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p21 2: 47408478 (GRCh38) [ NCBI UCSC ] 2: 47635617 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 24, 2015 Mar 10, 2024 Sep 5, 2013 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.289C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Gln97Ter nonsense NM_001258281.1:c.91C>T NP_001245210.1:p.Gln31Ter nonsense NC_000002.12:g.47408478C>T NC_000002.11:g.47635617C>T NG_007110.2:g.10355C>T LRG_218:g.10355C>T LRG_218t1:c.289C>T LRG_218p1:p.Gln97Ter - Protein change
- Q97*, Q31*
- Other names
- p.Q97*:CAG>TAG
- Canonical SPDI
- NC_000002.12:47408477:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MSH2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
7200 | 7352 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
reviewed by expert panel
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Sep 5, 2013 | RCV000076556.4 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2023 | RCV000160586.13 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 22, 2023 | RCV000409729.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 9, 2023 | RCV000491888.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 10, 2024 | RCV000699084.10 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Sep 05, 2013)
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reviewed by expert panel
Method: research
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Lynch Syndrome
Affected status: unknown
Allele origin:
germline
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International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000107585.3
First in ClinVar: Dec 19, 2013 Last updated: Dec 24, 2022 |
Comment:
Coding sequence variation resulting in a stop codon
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Pathogenic
(Nov 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Affected status: yes
Allele origin:
germline
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Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000781767.1
First in ClinVar: Jan 06, 2017 Last updated: Jan 06, 2017 |
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Pathogenic
(Oct 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000580464.5
First in ClinVar: Jun 25, 2017 Last updated: Nov 29, 2022 |
Comment:
The p.Q97* pathogenic mutation (also known as c.289C>T), located in coding exon 2 of the MSH2 gene, results from a C to T substitution at … (more)
The p.Q97* pathogenic mutation (also known as c.289C>T), located in coding exon 2 of the MSH2 gene, results from a C to T substitution at nucleotide position 289. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This mutation has been reported in multiple hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome families; several meeting Amsterdam criteria and at least one individual whose tumor demonstrated loss of MSH2 and MSH6 staining by immunohistochemistry (IHC) (Mangold E et al. J. Med. Genet., 2004 Jul;41:567-72; Dominguez-Valentin M et al. Hered Cancer Clin Pract, 2013 Dec;11:18; Siraj AK et al. Cancer, 2015 Jun;121:1762-71; Sjursen W et al. Mol Genet Genomic Med, 2016 Mar;4:223-31; Susswein LR et al. Genet Med, 2016 08;18:823-32; Dominguez-Valentin M et al. Front Oncol, 2016 Aug;6:189; Rossi BM et al. BMC Cancer, 2017 Sep;17:623; Ambry internal data). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Mar 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004018371.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Jan 10, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000827779.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln97*) in the MSH2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln97*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with colorectal cancer and clinical features of Lynch syndrome (PMID: 15235030, 24344984, 25712738, 26681312, 28874130). ClinVar contains an entry for this variant (Variation ID: 91054). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV001348702.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 2 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 2 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals and families affected with Lynch syndrome and Lynch syndrome-associated disease (PMID: 15235030, 24344984, 25712738, 26681312, 27606285, 28874130). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jul 28, 2014)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000211180.10
First in ClinVar: Feb 24, 2015 Last updated: May 29, 2016 |
Comment:
This pathogenic variant is denoted MSH2 c.289C>T at the cDNA level and p.Gln97Ter (Q97X) at the protein level. The substitution creates a nonsense variant, which … (more)
This pathogenic variant is denoted MSH2 c.289C>T at the cDNA level and p.Gln97Ter (Q97X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with Lynch syndrome (Mangold 2004). We therefore consider this variant to be pathogenic. (less)
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Pathogenic
(Jun 07, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450323.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Sep 09, 2016)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000489240.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002563566.9
First in ClinVar: Aug 23, 2022 Last updated: Mar 10, 2024 |
Comment:
MSH2: PVS1, PM2
Number of individuals with the variant: 3
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America. | Rossi BM | BMC cancer | 2017 | PMID: 28874130 |
MLH1 Ile219Val Polymorphism in Argentinean Families with Suspected Lynch Syndrome. | Dominguez-Valentin M | Frontiers in oncology | 2016 | PMID: 27606285 |
Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations. | Sjursen W | Molecular genetics & genomic medicine | 2016 | PMID: 27064304 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer. | Siraj AK | Cancer | 2015 | PMID: 25712738 |
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 |
Mutation spectrum in South American Lynch syndrome families. | Dominguez-Valentin M | Hereditary cancer in clinical practice | 2013 | PMID: 24344984 |
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 |
A genotype-phenotype correlation in HNPCC: strong predominance of msh2 mutations in 41 patients with Muir-Torre syndrome. | Mangold E | Journal of medical genetics | 2004 | PMID: 15235030 |
http://www.insight-database.org/classifications/index.html?gene=MSH2&variant=c.289C%3ET | - | - | - | - |
Text-mined citations for rs63750970 ...
HelpRecord last updated Mar 11, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.