ClinVar Genomic variation as it relates to human health
NM_001372051.1(CASP8):c.492_493del (p.Ala165fs)
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_001372051.1(CASP8):c.492_493del (p.Ala165fs)
Variation ID: 2762094 Accession: VCV002762094.1
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 2q33.1 2: 201272716-201272717 (GRCh38) [ NCBI UCSC ] 2: 202137439-202137440 (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 Feb 14, 2024 Feb 14, 2024 Jan 2, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001372051.1:c.492_493del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001358980.1:p.Ala165fs frameshift NM_001080124.2:c.492_493del NP_001073593.1:p.Ala165fs frameshift NM_001080125.2:c.669_670del NP_001073594.1:p.Ala224fs frameshift NM_001228.5:c.588_589del NP_001219.2:p.Ala197fs frameshift NM_001400642.1:c.669_670del NP_001387571.1:p.Ala224fs frameshift NM_001400645.1:c.492_493del NP_001387574.1:p.Ala165fs frameshift NM_001400648.1:c.492_493del NP_001387577.1:p.Ala165fs frameshift NM_001400651.1:c.492_493del NP_001387580.1:p.Ala165fs frameshift NM_001400653.1:c.492_493del NP_001387582.1:p.Ala165fs frameshift NM_001400654.1:c.492_493del NP_001387583.1:p.Ala165fs frameshift NM_001400655.1:c.492_493del NP_001387584.1:p.Ala165fs frameshift NM_001400656.1:c.492_493del NP_001387585.1:p.Ala165fs frameshift NM_001400657.1:c.492_493del NP_001387586.1:p.Ala165fs frameshift NM_001400658.1:c.492_493del NP_001387587.1:p.Ala165fs frameshift NM_001400659.1:c.492_493del NP_001387588.1:p.Ala165fs frameshift NM_001400660.1:c.492_493del NP_001387589.1:p.Ala165fs frameshift NM_001400661.1:c.492_493del NP_001387590.1:p.Ala165fs frameshift NM_001400662.1:c.492_493del NP_001387591.1:p.Ala165fs frameshift NM_001400663.1:c.492_493del NP_001387592.1:p.Ala165fs frameshift NM_001400664.1:c.492_493del NP_001387593.1:p.Ala165fs frameshift NM_001400665.1:c.669_670del NP_001387594.1:p.Ala224fs frameshift NM_001400666.1:c.492_493del NP_001387595.1:p.Ala165fs frameshift NM_001400667.1:c.492_493del NP_001387596.1:p.Ala165fs frameshift NM_001400668.1:c.492_493del NP_001387597.1:p.Ala165fs frameshift NM_001400669.1:c.183_184del NP_001387598.1:p.Ala62fs frameshift NM_001400670.1:c.492_493del NP_001387599.1:p.Ala165fs frameshift NM_001400671.1:c.-43TG[1] 5 prime UTR NM_001400672.1:c.-43TG[1] 5 prime UTR NM_001400673.1:c.-43TG[1] 5 prime UTR NM_001400674.1:c.-224TG[1] 5 prime UTR NM_001400675.1:c.-43TG[1] 5 prime UTR NM_001400676.1:c.-43TG[1] 5 prime UTR NM_001400677.1:c.-43TG[1] 5 prime UTR NM_001400678.1:c.-43TG[1] 5 prime UTR NM_001400679.1:c.492_493del NP_001387608.1:p.Ala165fs frameshift NM_001400680.1:c.-122TG[1] 5 prime UTR NM_001400750.1:c.-43TG[1] 5 prime UTR NM_001400751.1:c.-43TG[1] 5 prime UTR NM_033355.4:c.492_493del NP_203519.1:p.Ala165fs frameshift NM_033356.4:c.492_493del NP_203520.1:p.Ala165fs frameshift NR_111983.2:n.864TG[1] non-coding transcript variant NR_174564.1:n.488TG[1] non-coding transcript variant NR_174565.1:n.573TG[1] non-coding transcript variant NR_174581.1:n.599TG[1] non-coding transcript variant NR_174583.1:n.705TG[1] non-coding transcript variant NR_174584.1:n.864TG[1] non-coding transcript variant NR_174585.1:n.636TG[1] non-coding transcript variant NR_174586.1:n.610TG[1] non-coding transcript variant NR_174588.1:n.773TG[1] non-coding transcript variant NR_174589.1:n.568TG[1] non-coding transcript variant NR_174590.1:n.705TG[1] non-coding transcript variant NR_174591.1:n.636TG[1] non-coding transcript variant NR_174592.1:n.838TG[1] non-coding transcript variant NR_174593.1:n.636TG[1] non-coding transcript variant NR_174594.1:n.679TG[1] non-coding transcript variant NR_174595.1:n.594TG[1] non-coding transcript variant NR_174596.1:n.594TG[1] non-coding transcript variant NR_174597.1:n.594_595TG[1] NR_174598.1:n.773TG[1] non-coding transcript variant NR_174599.1:n.594TG[1] non-coding transcript variant NR_174600.1:n.864TG[1] non-coding transcript variant NR_174601.1:n.610TG[1] non-coding transcript variant NR_174602.1:n.594TG[1] non-coding transcript variant NC_000002.12:g.201272716TG[1] NC_000002.11:g.202137439TG[1] NG_007497.1:g.44259TG[1] LRG_34:g.44259TG[1] LRG_34t1:c.586_587TG[1] LRG_34p1:p.Ala197Profs LRG_34t2:c.490_491TG[1] LRG_34p2:p.Ala165Profs LRG_34t3:c.492_493del LRG_34p3:p.Ala165fs - Protein change
- A197fs, A62fs, A165fs, A224fs
- Other names
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- Canonical SPDI
- NC_000002.12:201272715:TGTG:TG
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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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CASP8 | - | - |
GRCh38 GRCh37 |
317 | 359 |
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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Pathogenic (1) |
criteria provided, single submitter
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Jan 2, 2024 | RCV003510173.1 |
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
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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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Pathogenic
(Jan 02, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autoimmune lymphoproliferative syndrome type 2B
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004325228.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ala197Profs*14) in the CASP8 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ala197Profs*14) in the CASP8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CASP8 are known to be pathogenic (PMID: 12353035, 25814141). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CASP8-related conditions. For these reasons, this variant has been classified as Pathogenic. (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
HelpTitle | Author | Journal | Year | Link |
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Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings. | Niemela J | Journal of clinical immunology | 2015 | PMID: 25814141 |
Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. | Chun HJ | Nature | 2002 | PMID: 12353035 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 20, 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.