ClinVar Miner

Submissions for variant NM_024537.4(CARS2):c.244G>A (p.Val82Ile)

gnomAD frequency: 0.00055  dbSNP: rs117788141
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000652709 SCV000774580 uncertain significance Combined oxidative phosphorylation defect type 27 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 82 of the CARS2 protein (p.Val82Ile). This variant is present in population databases (rs117788141, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. 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: 542307). 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 CARS2 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.
GeneDx RCV001592823 SCV001823968 likely benign not provided 2021-08-13 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000652709 SCV003830591 uncertain significance Combined oxidative phosphorylation defect type 27 2019-04-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003994066 SCV004813257 uncertain significance not specified 2024-02-19 criteria provided, single submitter clinical testing Variant summary: CARS2 c.244G>A (p.Val82Ile) results in a conservative amino acid change located in the catalytic domain (IPR032678) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 (i.e. in 1418 heterozygotes) in 1606264 control chromosomes (gnomAD v4.0). To our knowledge, no occurrence of c.244G>A 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: 542307). Based on the evidence outlined above, the variant was classified as uncertain significance.

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