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: 5
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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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000767915 SCV001407774 uncertain significance Autoimmune lymphoproliferative syndrome type 2B 2024-09-11 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). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CASP8 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV004965729 SCV005548347 uncertain significance Inborn genetic diseases 2024-11-14 criteria provided, single submitter clinical testing The c.159G>A (p.M53I) alteration is located in exon 3 (coding exon 1) of the CASP8 gene. This alteration results from a G to A substitution at nucleotide position 159, causing the methionine (M) at amino acid position 53 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV003224393 SCV005648031 uncertain significance Familial cancer of breast; Autoimmune lymphoproliferative syndrome type 2B; Hepatocellular carcinoma; Lung cancer 2024-06-16 criteria provided, single submitter clinical testing

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