ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.187del (p.Gly62_Val63insTer)
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.187del (p.Gly62_Val63insTer)
Variation ID: 90808 Accession: VCV000090808.19
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p21 2: 47403374 (GRCh38) [ NCBI UCSC ] 2: 47630513 (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 Feb 14, 2024 Sep 5, 2013 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.187del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Gly62_Val63insTer nonsense NM_000251.1:c.187delG NM_000251.2:c.187delG NM_001258281.1:c.-12del 5 prime UTR NC_000002.12:g.47403378del NC_000002.11:g.47630517del NG_007110.2:g.5255del LRG_218:g.5255del LRG_218t1:c.187del LRG_218p1:p.Gly62_Val63insTer - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:47403373:GGGGG:GGGG
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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
Help
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
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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 (2) |
reviewed by expert panel
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Sep 5, 2013 | RCV000076310.5 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 22, 2019 | RCV000202123.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 30, 2021 | RCV000491017.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 29, 2021 | RCV001231661.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 26, 2023 | RCV003452865.1 |
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
Help
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
Help
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: SCV000107331.3
First in ClinVar: Dec 19, 2013 Last updated: Dec 24, 2022 |
Comment:
Coding sequence variation introducing premature termination codon
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Pathogenic
(Jan 30, 2019)
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criteria provided, single submitter
Method: research
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Lynch syndrome
Affected status: yes
Allele origin:
germline
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A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center
Accession: SCV000914296.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Number of individuals with the variant: 1
Geographic origin: Brazil
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Pathogenic
(Sep 30, 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: SCV000580445.5
First in ClinVar: Jun 25, 2017 Last updated: Nov 29, 2022 |
Comment:
The c.187delG pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 187, causing … (more)
The c.187delG pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 187, causing a translational frameshift with a predicted alternate stop codon (p.V63*). This mutation has been reported in multiple HNPCC/Lynch syndrome patients; several whose tumors demonstrated loss of MSH2 staining by immunohistochemistry (IHC) (Behrens P et al. Int. J. Cancer, 2003 Nov;107:183-8; Mangold E et al. J Pathol, 2005 Dec;207:385-95; Dominguez-Valentin M et al. Hered Cancer Clin Pract, 2013 Dec;11:18; Carneiro da Silva F et al. PLoS One, 2015 Oct;10:e0139753; Lagerstedt-Robinson K et al. Oncol Rep, 2016 Nov;36:2823-2835; Rossi BM et al. BMC Cancer, 2017 Sep;17:623; Wischhusen JW et al. Cancer Epidemiol Biomarkers Prev, 2020 01;29:193-199). This mutation was also identified in an individual diagnosed with breast cancer at age 55, whose breast tumor showed microsatellite instability and absent MSH2 and MSH6 staining on IHC (Lotsari JE et al. Breast Cancer Res. 2012 Jun 12;14(3):R90). 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
(Jul 26, 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: SCV004188132.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 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
(Sep 18, 2018)
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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: SCV000293285.10
First in ClinVar: Jul 24, 2016 Last updated: Jul 24, 2016 |
Comment:
This deletion of one nucleotide is denoted MSH2 c.187delG at the cDNA level and p.Val63Ter (V63X) at the protein level. The normal sequence, with the … (more)
This deletion of one nucleotide is denoted MSH2 c.187delG at the cDNA level and p.Val63Ter (V63X) at the protein level. The normal sequence, with the base that is deleted in brackets, is AGGGG[delG]TGAT. The deletion creates a nonsense variant, which changes a Valine to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The International Society for Gastrointestinal Hereditary Tumours Incorporated (InSiGHT) classifies this variant as pathogenic (Thompson 2014). MSH2 c.187delG has been identified in individuals with a personal and family history suggestive of Lynch syndrome, and tumors from several of these individuals exhibited microsatellite instability and/or absence of MSH2 expression (Beherns 2003, Mangold 2005, Lotsari 2012). We consider this variant to be pathogenic. (less)
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Pathogenic
(Oct 22, 2019)
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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: SCV001449969.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Sep 29, 2021)
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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: SCV001404190.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 90808). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 90808). This premature translational stop signal has been observed in individual(s) with breast cancer and Lynch syndrome (PMID: 15849733, 22691310, 26437257, 27601186). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val63*) 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). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000257156.1
First in ClinVar: Nov 20, 2015 Last updated: Nov 20, 2015 |
Number of individuals with the variant: 1
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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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Clinical Factors Associated with Urinary Tract Cancer in Individuals with Lynch Syndrome. | Wischhusen JW | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2020 | PMID: 31615790 |
A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America. | Rossi BM | BMC cancer | 2017 | PMID: 28874130 |
Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population. | Lagerstedt-Robinson K | Oncology reports | 2016 | PMID: 27601186 |
Clinical and Molecular Characterization of Brazilian Patients Suspected to Have Lynch Syndrome. | Carneiro da Silva F | PloS one | 2015 | PMID: 26437257 |
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 |
Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases. | Lotsari JE | Breast cancer research : BCR | 2012 | PMID: 22691310 |
Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining. | Mangold E | The Journal of pathology | 2005 | PMID: 16216036 |
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 |
Stromal expression of invasion-promoting, matrix-degrading proteases MMP-1 and -9 and the Ets 1 transcription factor in HNPCC carcinomas and sporadic colorectal cancers. | Behrens P | International journal of cancer | 2003 | PMID: 12949792 |
http://www.insight-database.org/classifications/index.html?gene=MSH2&variant=c.187del | - | - | - | - |
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Text-mined citations for rs63750160 ...
HelpRecord last updated Feb 14, 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.