For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala765Leufs*47) 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).
ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.2293del (p.Ala765fs)
Germline
Classification
Help
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.
(1)
Help
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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000251.3(MSH2):c.2293del (p.Ala765fs)
Variation ID: 2109826 Accession: VCV002109826.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p21 2: 47478352 (GRCh38) [ NCBI UCSC ] 2: 47705491 (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 Feb 8, 2023 Feb 20, 2024 Mar 12, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000251.3:c.2293del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Ala765fs frameshift NM_001258281.1:c.2095del NP_001245210.1:p.Ala699fs frameshift NM_001406631.1:c.2293delG NP_001393560.1:p.Ala765Leufs frameshift NM_001406632.1:c.2293delG NP_001393561.1:p.Ala765Leufs frameshift NM_001406633.1:c.2293delG NP_001393562.1:p.Ala765Leufs frameshift NM_001406634.1:c.2293delG NP_001393563.1:p.Ala765Leufs frameshift NM_001406635.1:c.2293delG NP_001393564.1:p.Ala765Leufs frameshift NM_001406636.1:c.2260delG NP_001393565.1:p.Ala754Leufs frameshift NM_001406637.1:c.2293delG NP_001393566.1:p.Ala765Leufs frameshift NM_001406638.1:c.2332delG NP_001393567.1:p.Ala778Leufs frameshift NM_001406639.1:c.2293delG NP_001393568.1:p.Ala765Leufs frameshift NM_001406640.1:c.2293delG NP_001393569.1:p.Ala765Leufs frameshift NM_001406641.1:c.2293delG NP_001393570.1:p.Ala765Leufs frameshift NM_001406642.1:c.2293delG NP_001393571.1:p.Ala765Leufs frameshift NM_001406643.1:c.2293delG NP_001393572.1:p.Ala765Leufs frameshift NM_001406644.1:c.2293delG NP_001393573.1:p.Ala765Leufs frameshift NM_001406645.1:c.2293delG NP_001393574.1:p.Ala765Leufs frameshift NM_001406646.1:c.2293delG NP_001393575.1:p.Ala765Leufs frameshift NM_001406647.1:c.2143delG NP_001393576.1:p.Ala715Leufs frameshift NM_001406648.1:c.2293delG NP_001393577.1:p.Ala765Leufs frameshift NM_001406649.1:c.2143delG NP_001393578.1:p.Ala715Leufs frameshift NM_001406650.1:c.2143delG NP_001393579.1:p.Ala715Leufs frameshift NM_001406651.1:c.2143delG NP_001393580.1:p.Ala715Leufs frameshift NM_001406652.1:c.2143delG NP_001393581.1:p.Ala715Leufs frameshift NM_001406653.1:c.2233delG NP_001393582.1:p.Ala745Leufs frameshift NM_001406654.1:c.1873delG NP_001393583.1:p.Ala625Leufs frameshift NM_001406656.1:c.1396delG NP_001393585.1:p.Ala466Leufs frameshift NM_001406658.1:c.937delG NP_001393587.1:p.Ala313Leufs frameshift NM_001406659.1:c.937delG NP_001393588.1:p.Ala313Leufs frameshift NM_001406660.1:c.937delG NP_001393589.1:p.Ala313Leufs frameshift NM_001406661.1:c.937delG NP_001393590.1:p.Ala313Leufs frameshift NM_001406662.1:c.937delG NP_001393591.1:p.Ala313Leufs frameshift NM_001406669.1:c.937delG NP_001393598.1:p.Ala313Leufs frameshift NM_001406674.1:c.2293delG NP_001393603.1:p.Ala765Leufs frameshift NR_176230.1:n.2329delG NR_176231.1:n.2297delG NR_176232.1:n.2329delG NR_176233.1:n.2171delG NR_176234.1:n.2329delG NR_176235.1:n.2329delG NR_176236.1:n.2329delG NR_176237.1:n.2329delG NR_176238.1:n.2462delG NR_176239.1:n.2329delG NR_176240.1:n.2124delG NR_176241.1:n.2329delG NR_176242.1:n.2329delG NR_176243.1:n.2179delG NR_176244.1:n.2329delG NR_176245.1:n.2329delG NR_176246.1:n.2329delG NR_176247.1:n.2329delG NR_176248.1:n.2329delG NR_176249.1:n.2559delG NR_176250.1:n.2069delG NC_000002.12:g.47478354del NC_000002.11:g.47705493del NG_007110.2:g.80231del LRG_218:g.80231del LRG_218t1:c.2293del LRG_218p1:p.Ala765Leufs - Protein change
- A765fs, A699fs
- Other names
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- Canonical SPDI
- NC_000002.12:47478351:GGG:GG
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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
Help
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
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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
Help
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 |
7404 | 7566 | |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Mar 12, 2022 | RCV003031956.3 |
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
(Mar 12, 2022)
|
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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003330482.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala765Leufs*47) 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)
|
Comment:
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. |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala765Leufs*47) 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).
Citations for germline classification of 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 |
| 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 Sep 29, 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.