The c.1737delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1737, causing a translational frameshift with a predicted alternate stop codon (p.E580Kfs*10). 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.1737del (p.Glu580fs)
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.1737del (p.Glu580fs)
Variation ID: 1779107 Accession: VCV001779107.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p21 2: 47471038 (GRCh38) [ NCBI UCSC ] 2: 47698177 (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 Aug 4, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000251.3:c.1737del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Glu580fs frameshift NM_001258281.1:c.1539del NP_001245210.1:p.Glu514fs frameshift NM_001406631.1:c.1737delA NP_001393560.1:p.Glu580Lysfs frameshift NM_001406632.1:c.1737delA NP_001393561.1:p.Glu580Lysfs frameshift NM_001406633.1:c.1737delA NP_001393562.1:p.Glu580Lysfs frameshift NM_001406634.1:c.1737delA NP_001393563.1:p.Glu580Lysfs frameshift NM_001406635.1:c.1737delA NP_001393564.1:p.Glu580Lysfs frameshift NM_001406636.1:c.1704delA NP_001393565.1:p.Glu569Lysfs frameshift NM_001406637.1:c.1737delA NP_001393566.1:p.Glu580Lysfs frameshift NM_001406638.1:c.1776delA NP_001393567.1:p.Glu593Lysfs frameshift NM_001406639.1:c.1737delA NP_001393568.1:p.Glu580Lysfs frameshift NM_001406640.1:c.1737delA NP_001393569.1:p.Glu580Lysfs frameshift NM_001406641.1:c.1737delA NP_001393570.1:p.Glu580Lysfs frameshift NM_001406642.1:c.1737delA NP_001393571.1:p.Glu580Lysfs frameshift NM_001406643.1:c.1737delA NP_001393572.1:p.Glu580Lysfs frameshift NM_001406644.1:c.1737delA NP_001393573.1:p.Glu580Lysfs frameshift NM_001406645.1:c.1737delA NP_001393574.1:p.Glu580Lysfs frameshift NM_001406646.1:c.1737delA NP_001393575.1:p.Glu580Lysfs frameshift NM_001406647.1:c.1587delA NP_001393576.1:p.Glu530Lysfs frameshift NM_001406648.1:c.1737delA NP_001393577.1:p.Glu580Lysfs frameshift NM_001406649.1:c.1587delA NP_001393578.1:p.Glu530Lysfs frameshift NM_001406650.1:c.1587delA NP_001393579.1:p.Glu530Lysfs frameshift NM_001406651.1:c.1587delA NP_001393580.1:p.Glu530Lysfs frameshift NM_001406652.1:c.1587delA NP_001393581.1:p.Glu530Lysfs frameshift NM_001406653.1:c.1677delA NP_001393582.1:p.Glu560Lysfs frameshift NM_001406654.1:c.1317delA NP_001393583.1:p.Glu440Lysfs frameshift NM_001406655.1:c.1737delA NP_001393584.1:p.Glu580Lysfs frameshift NM_001406656.1:c.840delA NP_001393585.1:p.Glu281Lysfs frameshift NM_001406658.1:c.381delA NP_001393587.1:p.Glu128Lysfs frameshift NM_001406659.1:c.381delA NP_001393588.1:p.Glu128Lysfs frameshift NM_001406660.1:c.381delA NP_001393589.1:p.Glu128Lysfs frameshift NM_001406661.1:c.381delA NP_001393590.1:p.Glu128Lysfs frameshift NM_001406662.1:c.381delA NP_001393591.1:p.Glu128Lysfs frameshift NM_001406669.1:c.381delA NP_001393598.1:p.Glu128Lysfs frameshift NM_001406674.1:c.1737delA NP_001393603.1:p.Glu580Lysfs frameshift NR_176230.1:n.1773delA NR_176231.1:n.1773delA NR_176232.1:n.1773delA NR_176233.1:n.1615delA NR_176234.1:n.1773delA NR_176235.1:n.1773delA NR_176236.1:n.1773delA NR_176237.1:n.1773delA NR_176238.1:n.1906delA NR_176239.1:n.1773delA NR_176240.1:n.1773delA NR_176241.1:n.1773delA NR_176242.1:n.1773delA NR_176243.1:n.1623delA NR_176244.1:n.1773delA NR_176245.1:n.1773delA NR_176246.1:n.1773delA NR_176247.1:n.1773delA NR_176248.1:n.1773delA NR_176249.1:n.2003delA NR_176250.1:n.1513delA NC_000002.12:g.47471040del NC_000002.11:g.47698179del NG_007110.2:g.72917del LRG_218:g.72917del LRG_218t1:c.1737del LRG_218p1:p.Glu580Lysfs - Protein change
- E514fs, E580fs
- Other names
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- Canonical SPDI
- NC_000002.12:47471037:AAA:AA
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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 | ||
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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
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
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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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Aug 4, 2022 | RCV002407462.2 |
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
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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
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
(Aug 04, 2022)
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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: SCV002715737.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.1737delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1737, causing … (more)
The c.1737delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1737, causing a translational frameshift with a predicted alternate stop codon (p.E580Kfs*10). 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.1737delA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1737, causing a translational frameshift with a predicted alternate stop codon (p.E580Kfs*10). 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.