The c.540_541delTA pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 540 to 541, causing a translational frameshift with a predicted alternate stop codon (p.D180Efs*2). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.540_541del (p.Asp180fs)
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.540_541del (p.Asp180fs)
Variation ID: 2587521 Accession: VCV002587521.2
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 2p21 2: 47410266-47410267 (GRCh38) [ NCBI UCSC ] 2: 47637405-47637406 (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 Oct 28, 2023 May 1, 2024 Jul 10, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000251.3:c.540_541del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Asp180fs frameshift NM_001258281.1:c.342_343del NP_001245210.1:p.Asp114fs frameshift NM_001406631.1:c.540_541del NP_001393560.1:p.Asp180fs frameshift NM_001406632.1:c.540_541del NP_001393561.1:p.Asp180fs frameshift NM_001406633.1:c.540_541del NP_001393562.1:p.Asp180fs frameshift NM_001406634.1:c.540_541del NP_001393563.1:p.Asp180fs frameshift NM_001406635.1:c.540_541del NP_001393564.1:p.Asp180fs frameshift NM_001406636.1:c.540_541del NP_001393565.1:p.Asp180fs frameshift NM_001406637.1:c.540_541del NP_001393566.1:p.Asp180fs frameshift NM_001406638.1:c.540_541del NP_001393567.1:p.Asp180fs frameshift NM_001406639.1:c.540_541del NP_001393568.1:p.Asp180fs frameshift NM_001406640.1:c.540_541del NP_001393569.1:p.Asp180fs frameshift NM_001406641.1:c.540_541del NP_001393570.1:p.Asp180fs frameshift NM_001406642.1:c.540_541del NP_001393571.1:p.Asp180fs frameshift NM_001406643.1:c.540_541del NP_001393572.1:p.Asp180fs frameshift NM_001406644.1:c.540_541del NP_001393573.1:p.Asp180fs frameshift NM_001406645.1:c.540_541del NP_001393574.1:p.Asp180fs frameshift NM_001406646.1:c.540_541del NP_001393575.1:p.Asp180fs frameshift NM_001406647.1:c.540_541del NP_001393576.1:p.Asp180fs frameshift NM_001406648.1:c.540_541del NP_001393577.1:p.Asp180fs frameshift NM_001406649.1:c.540_541del NP_001393578.1:p.Asp180fs frameshift NM_001406650.1:c.540_541del NP_001393579.1:p.Asp180fs frameshift NM_001406651.1:c.540_541del NP_001393580.1:p.Asp180fs frameshift NM_001406652.1:c.540_541del NP_001393581.1:p.Asp180fs frameshift NM_001406653.1:c.480_481del NP_001393582.1:p.Asp160fs frameshift NM_001406654.1:c.120_121del NP_001393583.1:p.Asp40fs frameshift NM_001406655.1:c.540_541del NP_001393584.1:p.Asp180fs frameshift NM_001406656.1:c.-456_-455del 5 prime UTR NM_001406657.1:c.540_541del NP_001393586.1:p.Asp180fs frameshift NM_001406658.1:c.-779_-778del 5 prime UTR NM_001406659.1:c.-929_-928del 5 prime UTR NM_001406660.1:c.-1126_-1125del 5 prime UTR NM_001406661.1:c.-1081_-1080del 5 prime UTR NM_001406662.1:c.-998_-997del 5 prime UTR NM_001406666.1:c.540_541del NP_001393595.1:p.Asp180fs frameshift NM_001406669.1:c.-929_-928del 5 prime UTR NM_001406672.1:c.540_541del NP_001393601.1:p.Asp180fs frameshift NM_001406674.1:c.540_541del NP_001393603.1:p.Asp180fs frameshift NR_176230.1:n.576_577del non-coding transcript variant NR_176231.1:n.576_577del non-coding transcript variant NR_176232.1:n.576_577del non-coding transcript variant NR_176233.1:n.568_569del non-coding transcript variant NR_176234.1:n.576_577del non-coding transcript variant NR_176235.1:n.576_577del non-coding transcript variant NR_176236.1:n.576_577del non-coding transcript variant NR_176237.1:n.576_577del non-coding transcript variant NR_176238.1:n.576_577del non-coding transcript variant NR_176239.1:n.576_577del non-coding transcript variant NR_176240.1:n.576_577del non-coding transcript variant NR_176241.1:n.576_577del non-coding transcript variant NR_176242.1:n.576_577del non-coding transcript variant NR_176243.1:n.576_577del non-coding transcript variant NR_176244.1:n.576_577del non-coding transcript variant NR_176245.1:n.576_577del non-coding transcript variant NR_176246.1:n.576_577del non-coding transcript variant NR_176247.1:n.576_577del non-coding transcript variant NR_176248.1:n.576_577del non-coding transcript variant NR_176249.1:n.576_577del non-coding transcript variant NR_176250.1:n.576_577del non-coding transcript variant NC_000002.12:g.47410267_47410268del NC_000002.11:g.47637406_47637407del NG_007110.2:g.12144_12145del LRG_218:g.12144_12145del LRG_218t1:c.540_541del LRG_218p1:p.Asp180Glufs - Protein change
- D114fs, D40fs, D160fs, D180fs
- Other names
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- Canonical SPDI
- NC_000002.12:47410265:ATA:A
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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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Jul 10, 2023 | RCV003360920.2 |
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
(Jul 10, 2023)
|
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: SCV004055860.2
First in ClinVar: Oct 28, 2023 Last updated: May 01, 2024 |
Comment:
The c.540_541delTA pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 540 to … (more)
The c.540_541delTA pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 540 to 541, causing a translational frameshift with a predicted alternate stop codon (p.D180Efs*2). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.540_541delTA pathogenic mutation, located in coding exon 3 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 540 to 541, causing a translational frameshift with a predicted alternate stop codon (p.D180Efs*2). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.