The c.2288delC pathogenic mutation, located in coding exon 14 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 2288, causing a translational frameshift with a predicted alternate stop codon (p.A763Dfs*49). 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.
ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.2288del (p.Ala763fs)
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)
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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.2288del (p.Ala763fs)
Variation ID: 1789046 Accession: VCV001789046.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p21 2: 47478349 (GRCh38) [ NCBI UCSC ] 2: 47705488 (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 Sep 22, 2020 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000251.3:c.2288del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Ala763fs frameshift NM_001258281.1:c.2090del NP_001245210.1:p.Ala697fs frameshift NM_001406631.1:c.2288delC NP_001393560.1:p.Ala763Aspfs frameshift NM_001406632.1:c.2288delC NP_001393561.1:p.Ala763Aspfs frameshift NM_001406633.1:c.2288delC NP_001393562.1:p.Ala763Aspfs frameshift NM_001406634.1:c.2288delC NP_001393563.1:p.Ala763Aspfs frameshift NM_001406635.1:c.2288delC NP_001393564.1:p.Ala763Aspfs frameshift NM_001406636.1:c.2255delC NP_001393565.1:p.Ala752Aspfs frameshift NM_001406637.1:c.2288delC NP_001393566.1:p.Ala763Aspfs frameshift NM_001406638.1:c.2327delC NP_001393567.1:p.Ala776Aspfs frameshift NM_001406639.1:c.2288delC NP_001393568.1:p.Ala763Aspfs frameshift NM_001406640.1:c.2288delC NP_001393569.1:p.Ala763Aspfs frameshift NM_001406641.1:c.2288delC NP_001393570.1:p.Ala763Aspfs frameshift NM_001406642.1:c.2288delC NP_001393571.1:p.Ala763Aspfs frameshift NM_001406643.1:c.2288delC NP_001393572.1:p.Ala763Aspfs frameshift NM_001406644.1:c.2288delC NP_001393573.1:p.Ala763Aspfs frameshift NM_001406645.1:c.2288delC NP_001393574.1:p.Ala763Aspfs frameshift NM_001406646.1:c.2288delC NP_001393575.1:p.Ala763Aspfs frameshift NM_001406647.1:c.2138delC NP_001393576.1:p.Ala713Aspfs frameshift NM_001406648.1:c.2288delC NP_001393577.1:p.Ala763Aspfs frameshift NM_001406649.1:c.2138delC NP_001393578.1:p.Ala713Aspfs frameshift NM_001406650.1:c.2138delC NP_001393579.1:p.Ala713Aspfs frameshift NM_001406651.1:c.2138delC NP_001393580.1:p.Ala713Aspfs frameshift NM_001406652.1:c.2138delC NP_001393581.1:p.Ala713Aspfs frameshift NM_001406653.1:c.2228delC NP_001393582.1:p.Ala743Aspfs frameshift NM_001406654.1:c.1868delC NP_001393583.1:p.Ala623Aspfs frameshift NM_001406656.1:c.1391delC NP_001393585.1:p.Ala464Aspfs frameshift NM_001406658.1:c.932delC NP_001393587.1:p.Ala311Aspfs frameshift NM_001406659.1:c.932delC NP_001393588.1:p.Ala311Aspfs frameshift NM_001406660.1:c.932delC NP_001393589.1:p.Ala311Aspfs frameshift NM_001406661.1:c.932delC NP_001393590.1:p.Ala311Aspfs frameshift NM_001406662.1:c.932delC NP_001393591.1:p.Ala311Aspfs frameshift NM_001406669.1:c.932delC NP_001393598.1:p.Ala311Aspfs frameshift NM_001406674.1:c.2288delC NP_001393603.1:p.Ala763Aspfs frameshift NR_176230.1:n.2324delC NR_176231.1:n.2292delC NR_176232.1:n.2324delC NR_176233.1:n.2166delC NR_176234.1:n.2324delC NR_176235.1:n.2324delC NR_176236.1:n.2324delC NR_176237.1:n.2324delC NR_176238.1:n.2457delC NR_176239.1:n.2324delC NR_176240.1:n.2119delC NR_176241.1:n.2324delC NR_176242.1:n.2324delC NR_176243.1:n.2174delC NR_176244.1:n.2324delC NR_176245.1:n.2324delC NR_176246.1:n.2324delC NR_176247.1:n.2324delC NR_176248.1:n.2324delC NR_176249.1:n.2554delC NR_176250.1:n.2064delC NC_000002.12:g.47478349del NC_000002.11:g.47705488del NG_007110.2:g.80226del LRG_218:g.80226del LRG_218t1:c.2288del LRG_218p1:p.Ala763Aspfs - Protein change
- A697fs, A763fs
- Other names
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- Canonical SPDI
- NC_000002.12:47478348:C:
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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. |
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| Pathogenic (1) |
criteria provided, single submitter
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Sep 22, 2020 | RCV002446194.2 |
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
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 22, 2020)
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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: SCV002736859.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.2288delC pathogenic mutation, located in coding exon 14 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 2288, causing … (more)
The c.2288delC pathogenic mutation, located in coding exon 14 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 2288, causing a translational frameshift with a predicted alternate stop codon (p.A763Dfs*49). 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)
|
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:
The c.2288delC pathogenic mutation, located in coding exon 14 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 2288, causing a translational frameshift with a predicted alternate stop codon (p.A763Dfs*49). 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.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 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.