Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001059993 | SCV001224651 | uncertain significance | Combined oxidative phosphorylation defect type 27 | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the CARS2 mRNA. The next in-frame methionine is located at codon 114. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 854861). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587031 | SCV005077149 | uncertain significance | not specified | 2024-04-19 | criteria provided, single submitter | clinical testing | Variant summary: CARS2 c.2T>G (p.Met1Arg) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. The next downstream in frame methionine is located at p.Met114. Two of three in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.2T>G in individuals affected with Combined Oxidative Phosphorylation Defect Type 27 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 854861). Based on the evidence outlined above, the variant was classified as uncertain significance. |