ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.2078del (p.Cys693fs)
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.2078del (p.Cys693fs)
Variation ID: 1785495 Accession: VCV001785495.3
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p21 2: 47476439 (GRCh38) [ NCBI UCSC ] 2: 47703578 (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 Nov 29, 2022 May 1, 2024 Dec 11, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.2078del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Cys693fs frameshift NM_001258281.1:c.1880del NP_001245210.1:p.Cys627fs frameshift NM_001406631.1:c.2078delG NP_001393560.1:p.Cys693Phefs frameshift NM_001406632.1:c.2078delG NP_001393561.1:p.Cys693Phefs frameshift NM_001406633.1:c.2078delG NP_001393562.1:p.Cys693Phefs frameshift NM_001406634.1:c.2078delG NP_001393563.1:p.Cys693Phefs frameshift NM_001406635.1:c.2078delG NP_001393564.1:p.Cys693Phefs frameshift NM_001406636.1:c.2045delG NP_001393565.1:p.Cys682Phefs frameshift NM_001406637.1:c.2078delG NP_001393566.1:p.Cys693Phefs frameshift NM_001406638.1:c.2117delG NP_001393567.1:p.Cys706Phefs frameshift NM_001406639.1:c.2078delG NP_001393568.1:p.Cys693Phefs frameshift NM_001406640.1:c.2078delG NP_001393569.1:p.Cys693Phefs frameshift NM_001406641.1:c.2078delG NP_001393570.1:p.Cys693Phefs frameshift NM_001406642.1:c.2078delG NP_001393571.1:p.Cys693Phefs frameshift NM_001406643.1:c.2078delG NP_001393572.1:p.Cys693Phefs frameshift NM_001406644.1:c.2078delG NP_001393573.1:p.Cys693Phefs frameshift NM_001406645.1:c.2078delG NP_001393574.1:p.Cys693Phefs frameshift NM_001406646.1:c.2078delG NP_001393575.1:p.Cys693Phefs frameshift NM_001406647.1:c.1928delG NP_001393576.1:p.Cys643Phefs frameshift NM_001406648.1:c.2078delG NP_001393577.1:p.Cys693Phefs frameshift NM_001406649.1:c.1928delG NP_001393578.1:p.Cys643Phefs frameshift NM_001406650.1:c.1928delG NP_001393579.1:p.Cys643Phefs frameshift NM_001406651.1:c.1928delG NP_001393580.1:p.Cys643Phefs frameshift NM_001406652.1:c.1928delG NP_001393581.1:p.Cys643Phefs frameshift NM_001406653.1:c.2018delG NP_001393582.1:p.Cys673Phefs frameshift NM_001406654.1:c.1658delG NP_001393583.1:p.Cys553Phefs frameshift NM_001406656.1:c.1181delG NP_001393585.1:p.Cys394Phefs frameshift NM_001406658.1:c.722delG NP_001393587.1:p.Cys241Phefs frameshift NM_001406659.1:c.722delG NP_001393588.1:p.Cys241Phefs frameshift NM_001406660.1:c.722delG NP_001393589.1:p.Cys241Phefs frameshift NM_001406661.1:c.722delG NP_001393590.1:p.Cys241Phefs frameshift NM_001406662.1:c.722delG NP_001393591.1:p.Cys241Phefs frameshift NM_001406669.1:c.722delG NP_001393598.1:p.Cys241Phefs frameshift NM_001406674.1:c.2078delG NP_001393603.1:p.Cys693Phefs frameshift NR_176230.1:n.2114delG NR_176231.1:n.2114delG NR_176232.1:n.2114delG NR_176233.1:n.1956delG NR_176234.1:n.2114delG NR_176235.1:n.2114delG NR_176236.1:n.2114delG NR_176237.1:n.2114delG NR_176238.1:n.2247delG NR_176239.1:n.2114delG NR_176241.1:n.2114delG NR_176242.1:n.2114delG NR_176243.1:n.1964delG NR_176244.1:n.2114delG NR_176245.1:n.2114delG NR_176246.1:n.2114delG NR_176247.1:n.2114delG NR_176248.1:n.2114delG NR_176249.1:n.2344delG NR_176250.1:n.1854delG NC_000002.12:g.47476439del NC_000002.11:g.47703578del NG_007110.2:g.78316del LRG_218:g.78316del LRG_218t1:c.2078del LRG_218p1:p.Cys693Phefs - Protein change
- C693fs, C627fs
- Other names
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- Canonical SPDI
- NC_000002.12:47476438:G:
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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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- Links
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
Help
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 |
7401 | 7563 |
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) |
criteria provided, single submitter
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Jun 30, 2021 | RCV002422244.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 11, 2023 | RCV004007395.2 |
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
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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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Likely Pathogenic
(Dec 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004840110.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
The c.2078del (p.Cys693Phefs*17) variant of the MSH2 gene creates an premature translation termination codon. It is expected to result in an absent or disrupted protein … (more)
The c.2078del (p.Cys693Phefs*17) variant of the MSH2 gene creates an premature translation termination codon. It is expected to result in an absent or disrupted protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). ClinVar has an entry for this variant (ID: 1785495). Truncating variants in MSH2 are known to be pathogenic (PMID: 15849733). Therefore, this variant is classified as likely pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jun 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: SCV002727750.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.2078delG pathogenic mutation, located in coding exon 13 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 2078, causing … (more)
The c.2078delG pathogenic mutation, located in coding exon 13 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 2078, causing a translational frameshift with a predicted alternate stop codon (p.C693Ffs*17). 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)
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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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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 |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 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.