ClinVar Miner

Submissions for variant NM_001372051.1(CASP8):c.159G>A (p.Met53Ile)

gnomAD frequency: 0.00006  dbSNP: rs200261147
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767915 SCV000898570 uncertain significance Autoimmune lymphoproliferative syndrome type 2B 2018-11-09 criteria provided, single submitter clinical testing 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.
Invitae RCV000767915 SCV001407774 uncertain significance Autoimmune lymphoproliferative syndrome type 2B 2022-10-03 criteria provided, single submitter clinical testing 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224393 SCV003919770 uncertain significance Familial cancer of breast; Autoimmune lymphoproliferative syndrome type 2B; Hepatocellular carcinoma; Lung cancer 2021-03-30 criteria provided, single submitter clinical testing 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.

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