ClinVar Genomic variation as it relates to human health
NM_001372051.1(CASP8):c.159G>A (p.Met53Ile)
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.159G>A (p.Met53Ile)
Variation ID: 625904 Accession: VCV000625904.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q33.1 2: 201266645 (GRCh38) [ NCBI UCSC ] 2: 202131368 (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 26, 2019 Apr 30, 2023 Oct 3, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001372051.1:c.159G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001358980.1:p.Met53Ile missense NM_001080124.2:c.159G>A NP_001073593.1:p.Met53Ile missense NM_001080125.2:c.336G>A NP_001073594.1:p.Met112Ile missense NM_001228.5:c.159G>A NP_001219.2:p.Met53Ile missense NM_001400642.1:c.336G>A NP_001387571.1:p.Met112Ile missense NM_001400645.1:c.159G>A NP_001387574.1:p.Met53Ile missense NM_001400648.1:c.159G>A NP_001387577.1:p.Met53Ile missense NM_001400651.1:c.159G>A NP_001387580.1:p.Met53Ile missense NM_001400653.1:c.159G>A NP_001387582.1:p.Met53Ile missense NM_001400654.1:c.159G>A NP_001387583.1:p.Met53Ile missense NM_001400655.1:c.159G>A NP_001387584.1:p.Met53Ile missense NM_001400656.1:c.159G>A NP_001387585.1:p.Met53Ile missense NM_001400657.1:c.159G>A NP_001387586.1:p.Met53Ile missense NM_001400658.1:c.159G>A NP_001387587.1:p.Met53Ile missense NM_001400659.1:c.159G>A NP_001387588.1:p.Met53Ile missense NM_001400660.1:c.159G>A NP_001387589.1:p.Met53Ile missense NM_001400661.1:c.159G>A NP_001387590.1:p.Met53Ile missense NM_001400662.1:c.159G>A NP_001387591.1:p.Met53Ile missense NM_001400663.1:c.159G>A NP_001387592.1:p.Met53Ile missense NM_001400664.1:c.159G>A NP_001387593.1:p.Met53Ile missense NM_001400665.1:c.336G>A NP_001387594.1:p.Met112Ile missense NM_001400666.1:c.159G>A NP_001387595.1:p.Met53Ile missense NM_001400667.1:c.159G>A NP_001387596.1:p.Met53Ile missense NM_001400668.1:c.159G>A NP_001387597.1:p.Met53Ile missense NM_001400669.1:c.-4-4871G>A intron variant NM_001400670.1:c.159G>A NP_001387599.1:p.Met53Ile missense NM_001400671.1:c.-374G>A 5 prime UTR NM_001400672.1:c.-227-4871G>A intron variant NM_001400673.1:c.-374G>A 5 prime UTR NM_001400674.1:c.-555G>A 5 prime UTR NM_001400675.1:c.-227-4871G>A intron variant NM_001400676.1:c.-374G>A 5 prime UTR NM_001400677.1:c.-374G>A 5 prime UTR NM_001400678.1:c.-374G>A 5 prime UTR NM_001400679.1:c.159G>A NP_001387608.1:p.Met53Ile missense NM_001400680.1:c.-453G>A 5 prime UTR NM_001400750.1:c.-374G>A 5 prime UTR NM_001400751.1:c.-374G>A 5 prime UTR NM_033355.4:c.159G>A NP_203519.1:p.Met53Ile missense NM_033356.4:c.159G>A NP_203520.1:p.Met53Ile missense NR_111983.2:n.533G>A non-coding transcript variant NR_174564.1:n.263G>A non-coding transcript variant NR_174565.1:n.348G>A non-coding transcript variant NR_174581.1:n.374G>A non-coding transcript variant NR_174583.1:n.374G>A non-coding transcript variant NR_174584.1:n.533G>A non-coding transcript variant NR_174585.1:n.305G>A non-coding transcript variant NR_174586.1:n.279G>A non-coding transcript variant NR_174588.1:n.442G>A non-coding transcript variant NR_174589.1:n.237G>A non-coding transcript variant NR_174590.1:n.374G>A non-coding transcript variant NR_174591.1:n.305G>A non-coding transcript variant NR_174592.1:n.507G>A non-coding transcript variant NR_174593.1:n.305G>A non-coding transcript variant NR_174594.1:n.348G>A non-coding transcript variant NR_174595.1:n.263G>A non-coding transcript variant NR_174596.1:n.263G>A non-coding transcript variant NR_174597.1:n.263G>A NR_174598.1:n.442G>A non-coding transcript variant NR_174599.1:n.263G>A non-coding transcript variant NR_174600.1:n.533G>A non-coding transcript variant NR_174601.1:n.279G>A non-coding transcript variant NR_174602.1:n.263G>A non-coding transcript variant NC_000002.12:g.201266645G>A NC_000002.11:g.202131368G>A NG_007497.1:g.38188G>A LRG_34:g.38188G>A LRG_34t1:c.159G>A LRG_34p1:p.Met53Ile LRG_34t2:c.159G>A LRG_34p2:p.Met53Ile LRG_34t3:c.159G>A LRG_34p3:p.Met53Ile - Protein change
- M53I, M112I
- Other names
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- Canonical SPDI
- NC_000002.12:201266644:G:A
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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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0.00040 (C)
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00010
- 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
Help
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 |
314 | 356 |
Conditions - Germline
Condition
Help
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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Oct 3, 2022 | RCV000767915.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 30, 2021 | RCV003224393.1 |
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
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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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Uncertain significance
(Nov 09, 2018)
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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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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000898570.1
First in ClinVar: Apr 26, 2019 Last updated: Apr 26, 2019 |
Comment:
CASP8 NM_001228.4 exon 3 p.Met53Ile (c.159G>A): This variant has not been reported in the literature and is present in 0.1% (36/34588) of Latino alleles in … (more)
CASP8 NM_001228.4 exon 3 p.Met53Ile (c.159G>A): This variant has not been reported in the literature and is present in 0.1% (36/34588) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-202131368-G-A), including 1 homozygote. This variant is present in ClinVar (Variation ID:533728). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
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Uncertain significance
(Oct 03, 2022)
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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: SCV001407774.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 53 of the CASP8 protein (p.Met53Ile). … (more)
This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 53 of the CASP8 protein (p.Met53Ile). This variant is present in population databases (rs200261147, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CASP8-related conditions. ClinVar contains an entry for this variant (Variation ID: 625904). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CASP8 protein function. 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)
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Uncertain significance
(Mar 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Autoimmune lymphoproliferative syndrome type 2B Hepatocellular carcinoma Lung cancer
Affected status: unknown
Allele origin:
germline
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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV003919770.1
First in ClinVar: Apr 30, 2023 Last updated: Apr 30, 2023 |
Comment:
CASP8 NM_001228.4 exon 3 p.Met53Ile (c.159G>A): This variant has not been reported in the literature and is present in 0.1% (36/34588) of Latino alleles in … (more)
CASP8 NM_001228.4 exon 3 p.Met53Ile (c.159G>A): This variant has not been reported in the literature and is present in 0.1% (36/34588) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-202131368-G-A), including 1 homozygote. This variant is present in ClinVar (Variation ID:533728). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (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 rs200261147 ...
HelpRecord last updated Oct 15, 2023
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.