ClinVar Miner

Submissions for variant NM_024678.6(NARS2):c.167A>G (p.Gln56Arg)

gnomAD frequency: 0.00005  dbSNP: rs201751992
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481204 SCV000572257 likely pathogenic not provided 2017-03-10 criteria provided, single submitter clinical testing The Q56R variant in the NARS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Q56R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q56R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some 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. The Q56R variant is a strong candidate for a pathogenic variant.
Institute of Human Genetics, University of Leipzig Medical Center RCV000779615 SCV001950043 uncertain significance Combined oxidative phosphorylation defect type 24 2021-07-16 criteria provided, single submitter clinical testing The variant was identified in a compound heterozygous state with the variant c.1291T>C, p.(Tyr431His) in a patient with a phenotype that was compatible with a NARS2-related disorder (epileptic encephalopathy).
Labcorp Genetics (formerly Invitae), Labcorp RCV000481204 SCV003461161 uncertain significance not provided 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 56 of the NARS2 protein (p.Gln56Arg). This variant is present in population databases (rs201751992, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of NARS2-related conditions (PMID: 30327238). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 422720). 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 NARS2 protein function with a positive 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.
Ambry Genetics RCV004023180 SCV004964646 uncertain significance Inborn genetic diseases 2021-08-23 criteria provided, single submitter clinical testing The c.167A>G (p.Q56R) alteration is located in exon 2 (coding exon 2) of the NARS2 gene. This alteration results from a A to G substitution at nucleotide position 167, causing the glutamine (Q) at amino acid position 56 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
OMIM RCV000779615 SCV000916294 pathogenic Combined oxidative phosphorylation defect type 24 2019-05-28 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.