The c.246_247delAAinsC pathogenic mutation, located in coding exon 2 of the MSH2 gene, results from the deletion of two nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.K82Nfs*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.246_247delinsC (p.Lys82fs)
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.246_247delinsC (p.Lys82fs)
Variation ID: 2587530 Accession: VCV002587530.2
- Type and length
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Indel, 2 bp
- Location
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Cytogenetic: 2p21 2: 47408435-47408436 (GRCh38) [ NCBI UCSC ] 2: 47635574-47635575 (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 21, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000251.3:c.246_247delinsC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Lys82fs frameshift NM_001258281.1:c.48_49delinsC NP_001245210.1:p.Lys16fs frameshift NM_001406631.1:c.246_247delinsC NP_001393560.1:p.Lys82fs frameshift NM_001406632.1:c.246_247delinsC NP_001393561.1:p.Lys82fs frameshift NM_001406633.1:c.246_247delinsC NP_001393562.1:p.Lys82fs frameshift NM_001406634.1:c.246_247delinsC NP_001393563.1:p.Lys82fs frameshift NM_001406635.1:c.246_247delinsC NP_001393564.1:p.Lys82fs frameshift NM_001406636.1:c.246_247delinsC NP_001393565.1:p.Lys82fs frameshift NM_001406637.1:c.246_247delinsC NP_001393566.1:p.Lys82fs frameshift NM_001406638.1:c.246_247delinsC NP_001393567.1:p.Lys82fs frameshift NM_001406639.1:c.246_247delinsC NP_001393568.1:p.Lys82fs frameshift NM_001406640.1:c.246_247delinsC NP_001393569.1:p.Lys82fs frameshift NM_001406641.1:c.246_247delinsC NP_001393570.1:p.Lys82fs frameshift NM_001406642.1:c.246_247delinsC NP_001393571.1:p.Lys82fs frameshift NM_001406643.1:c.246_247delinsC NP_001393572.1:p.Lys82fs frameshift NM_001406644.1:c.246_247delinsC NP_001393573.1:p.Lys82fs frameshift NM_001406645.1:c.246_247delinsC NP_001393574.1:p.Lys82fs frameshift NM_001406646.1:c.246_247delinsC NP_001393575.1:p.Lys82fs frameshift NM_001406647.1:c.246_247delinsC NP_001393576.1:p.Lys82fs frameshift NM_001406648.1:c.246_247delinsC NP_001393577.1:p.Lys82fs frameshift NM_001406649.1:c.246_247delinsC NP_001393578.1:p.Lys82fs frameshift NM_001406650.1:c.246_247delinsC NP_001393579.1:p.Lys82fs frameshift NM_001406651.1:c.246_247delinsC NP_001393580.1:p.Lys82fs frameshift NM_001406652.1:c.246_247delinsC NP_001393581.1:p.Lys82fs frameshift NM_001406653.1:c.212-26_212-25delinsC intron variant NM_001406654.1:c.-129-46_-129-45delinsC intron variant NM_001406655.1:c.246_247delinsC NP_001393584.1:p.Lys82fs frameshift NM_001406656.1:c.-750_-749delinsC 5 prime UTR NM_001406657.1:c.246_247delinsC NP_001393586.1:p.Lys82fs frameshift NM_001406658.1:c.-1073_-1072delinsC 5 prime UTR NM_001406659.1:c.-1223_-1222delinsC 5 prime UTR NM_001406660.1:c.-1420_-1419delinsC 5 prime UTR NM_001406661.1:c.-1375_-1374delinsC 5 prime UTR NM_001406662.1:c.-1292_-1291delinsC 5 prime UTR NM_001406666.1:c.246_247delinsC NP_001393595.1:p.Lys82fs frameshift NM_001406669.1:c.-1223_-1222delinsC 5 prime UTR NM_001406672.1:c.246_247delinsC NP_001393601.1:p.Lys82fs frameshift NM_001406674.1:c.246_247delinsC NP_001393603.1:p.Lys82fs frameshift NR_176230.1:n.282_283delinsC non-coding transcript variant NR_176231.1:n.282_283delinsC non-coding transcript variant NR_176232.1:n.282_283delinsC non-coding transcript variant NR_176233.1:n.274_275delinsC non-coding transcript variant NR_176234.1:n.282_283delinsC non-coding transcript variant NR_176235.1:n.282_283delinsC non-coding transcript variant NR_176236.1:n.282_283delinsC non-coding transcript variant NR_176237.1:n.282_283delinsC non-coding transcript variant NR_176238.1:n.282_283delinsC non-coding transcript variant NR_176239.1:n.282_283delinsC non-coding transcript variant NR_176240.1:n.282_283delinsC non-coding transcript variant NR_176241.1:n.282_283delinsC non-coding transcript variant NR_176242.1:n.282_283delinsC non-coding transcript variant NR_176243.1:n.282_283delinsC non-coding transcript variant NR_176244.1:n.282_283delinsC non-coding transcript variant NR_176245.1:n.282_283delinsC non-coding transcript variant NR_176246.1:n.282_283delinsC non-coding transcript variant NR_176247.1:n.282_283delinsC non-coding transcript variant NR_176248.1:n.282_283delinsC non-coding transcript variant NR_176249.1:n.282_283delinsC non-coding transcript variant NR_176250.1:n.282_283delinsC non-coding transcript variant NC_000002.12:g.47408435_47408436delinsC NC_000002.11:g.47635574_47635575delinsC NG_007110.2:g.10312_10313delinsC LRG_218:g.10312_10313delinsC LRG_218t1:c.246_247delAAinsC LRG_218p1:p.Lys82Asnfs - Protein change
- K82fs, K16fs
- Other names
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- Canonical SPDI
- NC_000002.12:47408434:AA: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. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
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Jul 21, 2023 | RCV003350731.2 |
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 21, 2023)
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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: SCV004055873.2
First in ClinVar: Oct 28, 2023 Last updated: May 01, 2024 |
Comment:
The c.246_247delAAinsC pathogenic mutation, located in coding exon 2 of the MSH2 gene, results from the deletion of two nucleotides and insertion of one nucleotide … (more)
The c.246_247delAAinsC pathogenic mutation, located in coding exon 2 of the MSH2 gene, results from the deletion of two nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.K82Nfs*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.246_247delAAinsC pathogenic mutation, located in coding exon 2 of the MSH2 gene, results from the deletion of two nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.K82Nfs*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.