ClinVar Miner

Submissions for variant NM_032977.4(CASP10):c.1202_1208del (p.Cys401fs)

gnomAD frequency: 0.00033  dbSNP: rs747900630
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001796762 SCV000765617 uncertain significance Autoimmune lymphoproliferative syndrome type 2A 2024-01-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys401Leufs*15) in the CASP10 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CASP10 cause disease. This variant is present in population databases (rs747900630, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with primary immunodeficiencies (PMID: 27577878, 27872624, 34329798). ClinVar contains an entry for this variant (Variation ID: 535760). 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.
Mendelics RCV000986974 SCV001136138 benign Autoimmune lymphoproliferative syndrome type 1 2019-05-28 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003403483 SCV004104156 uncertain significance CASP10-related disorder 2023-11-22 no assertion criteria provided clinical testing The CASP10 c.1202_1208del7 variant is predicted to result in a frameshift and premature protein termination (p.Cys401Leufs*15). This variant has been reported in the heterozygous state in individuals with primary immunodeficiency (Patient 9, Gallo et al. 2016. PubMed ID: 27872624; Repository Table E1, Patient 16.1, Stray-Pedersen et al. 2016. PubMed ID: 27577878; Patient C, Matas Pérez et al. 2021. PubMed ID: 34329798). Of note, in one of those patients, the variant was paternally inherited. This variant is reported in 0.13% of alleles in individuals of Latino descent in gnomAD, including one homozygous individual. While this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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