Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479749 | SCV004223478 | pathogenic | Combined oxidative phosphorylation defect type 24 | 2023-11-07 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exons 8-9 in the NARS2 gene. A presumed nomenclature of c.(822+1_823-1)_(959+1_960-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a frameshift in the NARS2 gene and to undergo nonsense mediated decay, a known mechanism of disease. The variant allele was found at a frequency of 0.00046 in 21694 control chromosomes (gnomAD, structural variants dataset). c.(822+1_823-1)_(959+1_960-1)del has been reported in the literature in the compound heterozygous state in individuals affected with clinical phenotypes consistent with Combined Oxidative Phosphorylation Deficiency 24 (e.g. Wang_2016, Kistol_2023). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36675121, 26402642). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |