The p.Arg39fs variant in MSH2 has not been previously reported in individuals with MSH2-associated cancers or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 39 and leads to a premature termination codon 43 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MSH2 gene is an established disease mechanism in Lynch syndrome. In summary, this variant meets criteria to be classified as pathogenic for Lynch syndrome in an autosomal dominant manner based upon the predicted impact to the protein and absence in controls.
ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.115dup (p.Arg39fs)
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.115dup (p.Arg39fs)
Variation ID: 3076037 Accession: VCV003076037.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 2p21 2: 47403304-47403305 (GRCh38) [ NCBI UCSC ] 2: 47630443-47630444 (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 Apr 20, 2024 Apr 20, 2024 Jan 28, 2019 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000251.3:c.115dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Arg39fs frameshift NM_001258281.1:c.-30-54dup intron variant NM_001406631.1:c.115dup NP_001393560.1:p.Arg39fs frameshift NM_001406632.1:c.115dup NP_001393561.1:p.Arg39fs frameshift NM_001406633.1:c.115dup NP_001393562.1:p.Arg39fs frameshift NM_001406634.1:c.115dup NP_001393563.1:p.Arg39fs frameshift NM_001406635.1:c.115dup NP_001393564.1:p.Arg39fs frameshift NM_001406636.1:c.115dup NP_001393565.1:p.Arg39fs frameshift NM_001406637.1:c.115dup NP_001393566.1:p.Arg39fs frameshift NM_001406638.1:c.115dup NP_001393567.1:p.Arg39fs frameshift NM_001406639.1:c.115dup NP_001393568.1:p.Arg39fs frameshift NM_001406640.1:c.115dup NP_001393569.1:p.Arg39fs frameshift NM_001406641.1:c.115dup NP_001393570.1:p.Arg39fs frameshift NM_001406642.1:c.115dup NP_001393571.1:p.Arg39fs frameshift NM_001406643.1:c.115dup NP_001393572.1:p.Arg39fs frameshift NM_001406644.1:c.115dup NP_001393573.1:p.Arg39fs frameshift NM_001406645.1:c.115dup NP_001393574.1:p.Arg39fs frameshift NM_001406646.1:c.115dup NP_001393575.1:p.Arg39fs frameshift NM_001406647.1:c.115dup NP_001393576.1:p.Arg39fs frameshift NM_001406648.1:c.115dup NP_001393577.1:p.Arg39fs frameshift NM_001406649.1:c.115dup NP_001393578.1:p.Arg39fs frameshift NM_001406650.1:c.115dup NP_001393579.1:p.Arg39fs frameshift NM_001406651.1:c.115dup NP_001393580.1:p.Arg39fs frameshift NM_001406652.1:c.115dup NP_001393581.1:p.Arg39fs frameshift NM_001406653.1:c.115dup NP_001393582.1:p.Arg39fs frameshift NM_001406654.1:c.-226dup 5 prime UTR NM_001406655.1:c.115dup NP_001393584.1:p.Arg39fs frameshift NM_001406656.1:c.-881dup 5 prime UTR NM_001406657.1:c.115dup NP_001393586.1:p.Arg39fs frameshift NM_001406658.1:c.-1204dup 5 prime UTR NM_001406659.1:c.-1354dup 5 prime UTR NM_001406660.1:c.-1551dup 5 prime UTR NM_001406661.1:c.-1506dup 5 prime UTR NM_001406662.1:c.-1423dup 5 prime UTR NM_001406666.1:c.115dup NP_001393595.1:p.Arg39fs frameshift NM_001406669.1:c.-1354dup 5 prime UTR NM_001406672.1:c.115dup NP_001393601.1:p.Arg39fs frameshift NM_001406674.1:c.115dup NP_001393603.1:p.Arg39fs frameshift NR_176230.1:n.151dup non-coding transcript variant NR_176231.1:n.151dup non-coding transcript variant NR_176232.1:n.151dup non-coding transcript variant NR_176233.1:n.151dup non-coding transcript variant NR_176234.1:n.151dup non-coding transcript variant NR_176235.1:n.151dup non-coding transcript variant NR_176236.1:n.151dup non-coding transcript variant NR_176237.1:n.151dup non-coding transcript variant NR_176238.1:n.151dup non-coding transcript variant NR_176239.1:n.151dup non-coding transcript variant NR_176240.1:n.151dup non-coding transcript variant NR_176241.1:n.151dup non-coding transcript variant NR_176242.1:n.151dup non-coding transcript variant NR_176243.1:n.151dup non-coding transcript variant NR_176244.1:n.151dup non-coding transcript variant NR_176245.1:n.151dup non-coding transcript variant NR_176246.1:n.151dup non-coding transcript variant NR_176247.1:n.151dup non-coding transcript variant NR_176248.1:n.151dup non-coding transcript variant NR_176249.1:n.151dup non-coding transcript variant NR_176250.1:n.151dup non-coding transcript variant NC_000002.12:g.47403306dup NC_000002.11:g.47630445dup NG_007110.2:g.5183dup NG_095167.1:g.510dup LRG_218:g.5183dup LRG_218t1:c.115dup LRG_218p1:p.Arg39Profs - Protein change
- R39fs
- Other names
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- Canonical SPDI
- NC_000002.12:47403304:CC:CCC
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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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Jan 28, 2019 | RCV004018355.2 |
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
(Jan 28, 2019)
|
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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848100.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Arg39fs variant in MSH2 has not been previously reported in individuals with MSH2-associated cancers or in large population studies. This variant is predicted to … (more)
The p.Arg39fs variant in MSH2 has not been previously reported in individuals with MSH2-associated cancers or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 39 and leads to a premature termination codon 43 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MSH2 gene is an established disease mechanism in Lynch syndrome. In summary, this variant meets criteria to be classified as pathogenic for Lynch syndrome in an autosomal dominant manner based upon the predicted impact to the protein and absence in controls. (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 p.Arg39fs variant in MSH2 has not been previously reported in individuals with MSH2-associated cancers or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 39 and leads to a premature termination codon 43 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MSH2 gene is an established disease mechanism in Lynch syndrome. In summary, this variant meets criteria to be classified as pathogenic for Lynch syndrome in an autosomal dominant manner based upon the predicted impact to the protein and absence in controls.
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 Jun 23, 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.