ClinVar Miner

Submissions for variant NM_020320.5(RARS2):c.970A>G (p.Thr324Ala)

gnomAD frequency: 0.00002  dbSNP: rs774506039
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199049 SCV000252166 uncertain significance not provided 2014-03-20 criteria provided, single submitter clinical testing p.Thr324Ala (ACC>GCC): c.970 A>G in exon 11 of the RARS2 gene (NM_020320.3) A variant of unknown significance has been identified in the RARS2 gene. The T324A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The T324A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LSME-MITOP panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000199049 SCV003481332 uncertain significance not provided 2022-08-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 324 of the RARS2 protein (p.Thr324Ala). This variant is present in population databases (rs774506039, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 215063). 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 expected to disrupt RARS2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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.
Natera, Inc. RCV001828030 SCV002079900 uncertain significance Pontocerebellar hypoplasia type 6 2019-11-11 no assertion criteria provided clinical testing

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