ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.2410_2411insT (p.Lys804fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.2410_2411insT (p.Lys804fs)
Variation ID: 3075845 Accession: VCV003075845.1
- Type and length
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Insertion, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47800393-47800394 (GRCh38) [ NCBI UCSC ] 2: 48027532-48027533 (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 Apr 1, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.2410_2411insT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Lys804fs frameshift NM_001281492.2:c.2020_2021insT NP_001268421.1:p.Lys674fs frameshift NM_001281493.2:c.1504_1505insT NP_001268422.1:p.Lys502fs frameshift NM_001281494.2:c.1504_1505insT NP_001268423.1:p.Lys502fs frameshift NM_001406795.1:c.2506_2507insT NP_001393724.1:p.Lys836fs frameshift NM_001406796.1:c.2410_2411insT NP_001393725.1:p.Lys804fs frameshift NM_001406797.1:c.2113_2114insT NP_001393726.1:p.Lys705fs frameshift NM_001406798.1:c.2410_2411insT NP_001393727.1:p.Lys804fs frameshift NM_001406799.1:c.1885_1886insT NP_001393728.1:p.Lys629fs frameshift NM_001406800.1:c.2410_2411insT NP_001393729.1:p.Lys804fs frameshift NM_001406801.1:c.2113_2114insT NP_001393730.1:p.Lys705fs frameshift NM_001406802.1:c.2506_2507insT NP_001393731.1:p.Lys836fs frameshift NM_001406803.1:c.2308+102_2308+103insT intron variant NM_001406804.1:c.2332_2333insT NP_001393733.1:p.Lys778fs frameshift NM_001406805.1:c.2113_2114insT NP_001393734.1:p.Lys705fs frameshift NM_001406806.1:c.1885_1886insT NP_001393735.1:p.Lys629fs frameshift NM_001406807.1:c.1885_1886insT NP_001393736.1:p.Lys629fs frameshift NM_001406808.1:c.2410_2411insT NP_001393737.1:p.Lys804fs frameshift NM_001406809.1:c.2410_2411insT NP_001393738.1:p.Lys804fs frameshift NM_001406811.1:c.1504_1505insT NP_001393740.1:p.Lys502fs frameshift NM_001406812.1:c.1504_1505insT NP_001393741.1:p.Lys502fs frameshift NM_001406813.1:c.2416_2417insT NP_001393742.1:p.Lys806fs frameshift NM_001406814.1:c.1504_1505insT NP_001393743.1:p.Lys502fs frameshift NM_001406815.1:c.1504_1505insT NP_001393744.1:p.Lys502fs frameshift NM_001406816.1:c.1504_1505insT NP_001393745.1:p.Lys502fs frameshift NM_001406817.1:c.1606+804_1606+805insT intron variant NM_001406818.1:c.2113_2114insT NP_001393747.1:p.Lys705fs frameshift NM_001406819.1:c.2113_2114insT NP_001393748.1:p.Lys705fs frameshift NM_001406820.1:c.2113_2114insT NP_001393749.1:p.Lys705fs frameshift NM_001406821.1:c.2113_2114insT NP_001393750.1:p.Lys705fs frameshift NM_001406822.1:c.2113_2114insT NP_001393751.1:p.Lys705fs frameshift NM_001406823.1:c.1504_1505insT NP_001393752.1:p.Lys502fs frameshift NM_001406824.1:c.2113_2114insT NP_001393753.1:p.Lys705fs frameshift NM_001406825.1:c.2113_2114insT NP_001393754.1:p.Lys705fs frameshift NM_001406826.1:c.2242_2243insT NP_001393755.1:p.Lys748fs frameshift NM_001406827.1:c.2113_2114insT NP_001393756.1:p.Lys705fs frameshift NM_001406828.1:c.2113_2114insT NP_001393757.1:p.Lys705fs frameshift NM_001406829.1:c.1504_1505insT NP_001393758.1:p.Lys502fs frameshift NM_001406830.1:c.2113_2114insT NP_001393759.1:p.Lys705fs frameshift NM_001407362.1:c.628-273_628-272insT intron variant NR_176256.1:n.1272_1273insT non-coding transcript variant NR_176257.1:n.2499_2500insT non-coding transcript variant NR_176258.1:n.2499_2500insT non-coding transcript variant NR_176259.1:n.2499_2500insT non-coding transcript variant NR_176261.1:n.2499_2500insT non-coding transcript variant NC_000002.12:g.47800393_47800394insT NC_000002.11:g.48027532_48027533insT NG_007111.1:g.22247_22248insT LRG_219:g.22247_22248insT LRG_219t1:c.2410_2411insT LRG_219p1:p.Lys804Ilefs - Protein change
- K502fs, K629fs, K674fs, K705fs, K748fs, K778fs, K804fs, K806fs, K836fs
- Other names
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- Canonical SPDI
- NC_000002.12:47800393::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
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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
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
9153 | 9466 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Apr 1, 2022 | RCV004018163.2 |
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
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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
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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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Likely Pathogenic
(Apr 01, 2022)
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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: SCV004848645.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Lys804IlefsX16 variant in MSH6 has not been reported in individuals with MSH6-associated cancers or in large population databases. This variant is predicted to cause … (more)
The p.Lys804IlefsX16 variant in MSH6 has not been reported in individuals with MSH6-associated cancers or in large population databases. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 804 and leads to a premature termination codon 16 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MSH6 gene is an established disease mechanism in autosomal dominant Lynch syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. (less)
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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. |
Citations for germline classification of this variant
HelpThere 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.