The c.466delT pathogenic mutation, located in coding exon 3 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 466, causing a translational frameshift with a predicted alternate stop codon (p.S156Qfs*18). 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_000179.3(MSH6):c.466del (p.Ser156fs)
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.
(2)
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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
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.466del (p.Ser156fs)
Variation ID: 3230582 Accession: VCV003230582.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47795902 (GRCh38) [ NCBI UCSC ] 2: 48023041 (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 May 1, 2024 Jul 23, 2024 Jun 24, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.466del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Ser156fs frameshift NM_001281492.2:c.238-2709del intron variant NM_001281493.2:c.-279-2709del intron variant NM_001281494.2:c.-437del 5 prime UTR NM_001406795.1:c.562del NP_001393724.1:p.Ser188fs frameshift NM_001406796.1:c.466del NP_001393725.1:p.Ser156fs frameshift NM_001406797.1:c.169del NP_001393726.1:p.Ser57fs frameshift NM_001406798.1:c.466del NP_001393727.1:p.Ser156fs frameshift NM_001406799.1:c.-60del 5 prime UTR NM_001406800.1:c.466del NP_001393729.1:p.Ser156fs frameshift NM_001406801.1:c.169del NP_001393730.1:p.Ser57fs frameshift NM_001406802.1:c.562del NP_001393731.1:p.Ser188fs frameshift NM_001406803.1:c.466del NP_001393732.1:p.Ser156fs frameshift NM_001406804.1:c.388del NP_001393733.1:p.Ser130fs frameshift NM_001406805.1:c.169del NP_001393734.1:p.Ser57fs frameshift NM_001406806.1:c.-60del 5 prime UTR NM_001406807.1:c.-60del 5 prime UTR NM_001406808.1:c.466del NP_001393737.1:p.Ser156fs frameshift NM_001406809.1:c.466del NP_001393738.1:p.Ser156fs frameshift NM_001406811.1:c.-279-2709del intron variant NM_001406812.1:c.-279-2709del intron variant NM_001406813.1:c.472del NP_001393742.1:p.Ser158fs frameshift NM_001406814.1:c.-529del 5 prime UTR NM_001406815.1:c.-279-2709del intron variant NM_001406816.1:c.-279-2709del intron variant NM_001406817.1:c.466del NP_001393746.1:p.Ser156fs frameshift NM_001406818.1:c.169del NP_001393747.1:p.Ser57fs frameshift NM_001406819.1:c.169del NP_001393748.1:p.Ser57fs frameshift NM_001406820.1:c.169del NP_001393749.1:p.Ser57fs frameshift NM_001406821.1:c.169del NP_001393750.1:p.Ser57fs frameshift NM_001406822.1:c.169del NP_001393751.1:p.Ser57fs frameshift NM_001406823.1:c.-279-2709del intron variant NM_001406824.1:c.169del NP_001393753.1:p.Ser57fs frameshift NM_001406825.1:c.169del NP_001393754.1:p.Ser57fs frameshift NM_001406826.1:c.298del NP_001393755.1:p.Ser100fs frameshift NM_001406827.1:c.169del NP_001393756.1:p.Ser57fs frameshift NM_001406828.1:c.169del NP_001393757.1:p.Ser57fs frameshift NM_001406829.1:c.-279-2709del intron variant NM_001406830.1:c.169del NP_001393759.1:p.Ser57fs frameshift NM_001407362.1:c.466del NP_001394291.1:p.Ser156fs frameshift NR_176256.1:n.555del non-coding transcript variant NR_176257.1:n.555del non-coding transcript variant NR_176258.1:n.555del non-coding transcript variant NR_176259.1:n.555del non-coding transcript variant NR_176260.1:n.555delT NR_176261.1:n.555del non-coding transcript variant NC_000002.12:g.47795902del NC_000002.11:g.48023041del NG_007111.1:g.17756del LRG_219:g.17756del LRG_219t1:c.466del LRG_219p1:p.Ser156Glnfs - Protein change
- S100fs, S130fs, S156fs, S158fs, S188fs, S57fs
- Other names
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- Canonical SPDI
- NC_000002.12:47795901:T:
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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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| MSH6 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9161 | 9479 | |
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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Dec 11, 2023 | RCV004520733.1 | |
| Pathogenic (1) |
criteria provided, single submitter
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Jun 24, 2024 | RCV004588550.1 |
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
(Dec 11, 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: SCV005032907.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.466delT pathogenic mutation, located in coding exon 3 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 466, causing … (more)
The c.466delT pathogenic mutation, located in coding exon 3 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 466, causing a translational frameshift with a predicted alternate stop codon (p.S156Qfs*18). 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)
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Pathogenic
(Jun 24, 2024)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV005083703.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Comment:
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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.466delT pathogenic mutation, located in coding exon 3 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 466, causing a translational frameshift with a predicted alternate stop codon (p.S156Qfs*18). 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.
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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 Oct 08, 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.