This sequence change creates a premature translational stop signal (p.Arg449*) in the CASP8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the CASP8 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CASP8-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_001372051.1(CASP8):c.1294C>T (p.Arg432Ter)
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)
Help
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.
Uncertain significance
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_001372051.1(CASP8):c.1294C>T (p.Arg432Ter)
Variation ID: 2780013 Accession: VCV002780013.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q33.1 2: 201285307 (GRCh38) [ NCBI UCSC ] 2: 202150030 (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 20, 2024 Feb 20, 2024 Feb 14, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001372051.1:c.1294C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001358980.1:p.Arg432Ter nonsense NM_001080124.2:c.1249C>T NP_001073593.1:p.Arg417Ter nonsense NM_001080125.2:c.1471C>T NP_001073594.1:p.Arg491Ter nonsense NM_001228.5:c.1345C>T NP_001219.2:p.Arg449Ter nonsense NM_001400642.1:c.1426C>T NP_001387571.1:p.Arg476Ter nonsense NM_001400645.1:c.1327C>T NP_001387574.1:p.Arg443Ter nonsense NM_001400648.1:c.1294C>T NP_001387577.1:p.Arg432Ter nonsense NM_001400651.1:c.1294C>T NP_001387580.1:p.Arg432Ter nonsense NM_001400653.1:c.1294C>T NP_001387582.1:p.Arg432Ter nonsense NM_001400654.1:c.1294C>T NP_001387583.1:p.Arg432Ter nonsense NM_001400655.1:c.1294C>T NP_001387584.1:p.Arg432Ter nonsense NM_001400656.1:c.1294C>T NP_001387585.1:p.Arg432Ter nonsense NM_001400657.1:c.1294C>T NP_001387586.1:p.Arg432Ter nonsense NM_001400658.1:c.1249C>T NP_001387587.1:p.Arg417Ter nonsense NM_001400659.1:c.1249C>T NP_001387588.1:p.Arg417Ter nonsense NM_001400660.1:c.1249C>T NP_001387589.1:p.Arg417Ter nonsense NM_001400661.1:c.1249C>T NP_001387590.1:p.Arg417Ter nonsense NM_001400662.1:c.1249C>T NP_001387591.1:p.Arg417Ter nonsense NM_001400663.1:c.1249C>T NP_001387592.1:p.Arg417Ter nonsense NM_001400664.1:c.1225C>T NP_001387593.1:p.Arg409Ter nonsense NM_001400665.1:c.1219C>T NP_001387594.1:p.Arg407Ter nonsense NM_001400666.1:c.1087C>T NP_001387595.1:p.Arg363Ter nonsense NM_001400667.1:c.1042C>T NP_001387596.1:p.Arg348Ter nonsense NM_001400668.1:c.1042C>T NP_001387597.1:p.Arg348Ter nonsense NM_001400669.1:c.985C>T NP_001387598.1:p.Arg329Ter nonsense NM_001400670.1:c.847C>T NP_001387599.1:p.Arg283Ter nonsense NM_001400671.1:c.697C>T NP_001387600.1:p.Arg233Ter nonsense NM_001400672.1:c.697C>T NP_001387601.1:p.Arg233Ter nonsense NM_001400673.1:c.697C>T NP_001387602.1:p.Arg233Ter nonsense NM_001400674.1:c.679C>T NP_001387603.1:p.Arg227Ter nonsense NM_001400675.1:c.652C>T NP_001387604.1:p.Arg218Ter nonsense NM_001400676.1:c.652C>T NP_001387605.1:p.Arg218Ter nonsense NM_001400677.1:c.652C>T NP_001387606.1:p.Arg218Ter nonsense NM_001400678.1:c.652C>T NP_001387607.1:p.Arg218Ter nonsense NM_001400680.1:c.679C>T NP_001387609.1:p.Arg227Ter nonsense NM_001400750.1:c.697C>T NP_001387679.1:p.Arg233Ter nonsense NM_001400751.1:c.652C>T NP_001387680.1:p.Arg218Ter nonsense NM_033355.4:c.1294C>T NP_203519.1:p.Arg432Ter nonsense NM_033356.4:c.1249C>T NP_203520.1:p.Arg417Ter nonsense NR_111983.2:n.1804C>T non-coding transcript variant NR_174564.1:n.1383C>T non-coding transcript variant NR_174565.1:n.1513C>T non-coding transcript variant NR_174581.1:n.1539C>T non-coding transcript variant NR_174583.1:n.1645C>T non-coding transcript variant NR_174584.1:n.1558C>T non-coding transcript variant NR_174585.1:n.1576C>T non-coding transcript variant NR_174586.1:n.1550C>T non-coding transcript variant NR_174588.1:n.1713C>T non-coding transcript variant NR_174589.1:n.1508C>T non-coding transcript variant NR_174590.1:n.1600C>T non-coding transcript variant NR_174591.1:n.1531C>T non-coding transcript variant NR_174592.1:n.1876C>T non-coding transcript variant NR_174593.1:n.1674C>T non-coding transcript variant NR_174594.1:n.1717C>T non-coding transcript variant NR_174595.1:n.1632C>T non-coding transcript variant NR_174596.1:n.1469C>T non-coding transcript variant NR_174597.1:n.1469C>T NR_174598.1:n.1827C>T non-coding transcript variant NR_174599.1:n.1211C>T non-coding transcript variant NR_174600.1:n.1739C>T non-coding transcript variant NR_174601.1:n.1664C>T non-coding transcript variant NR_174602.1:n.1534C>T non-coding transcript variant NC_000002.12:g.201285307C>T NC_000002.11:g.202150030C>T NG_007497.1:g.56850C>T LRG_34:g.56850C>T LRG_34t1:c.1345C>T LRG_34p1:p.Arg449Ter LRG_34t2:c.1294C>T LRG_34p2:p.Arg432Ter LRG_34t3:c.1294C>T LRG_34p3:p.Arg432Ter - Protein change
- R227*, R233*, R363*, R409*, R443*, R283*, R329*, R348*, R417*, R407*, R432*, R476*, R491*, R218*, R449*
- Other names
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- Canonical SPDI
- NC_000002.12:201285306:C: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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| CASP8 | - | - |
GRCh38 GRCh37 |
321 | 363 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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Feb 14, 2023 | RCV003619911.2 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Feb 14, 2023)
|
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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004376058.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg449*) in the CASP8 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg449*) in the CASP8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the CASP8 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CASP8-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (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:
This sequence change creates a premature translational stop signal (p.Arg449*) in the CASP8 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the CASP8 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CASP8-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
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 Sep 30, 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.