Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000272507 | SCV000463664 | likely benign | Combined oxidative phosphorylation defect type 8 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| Gene |
RCV000417904 | SCV000518504 | likely benign | not provided | 2021-03-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000417904 | SCV001068481 | likely benign | not provided | 2024-11-04 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000417904 | SCV001553984 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The AARS2 p.Met362Leu variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs147091256), ClinVar (classified as a VUS by Illumina Clinical Services Laboratory and GeneDx; associated condition is Combined oxidative phosphorylation deficiency). The variant was identified in control databases in 191 of 282776 chromosomes at a frequency of 0.000675 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017) and was observed in the following populations: African in 170 of 24940 chromosomes (freq: 0.006816), Latino in 13 of 35434 chromosomes (freq: 0.000367), Other in 2 of 7228 chromosomes (freq: 0.000277) and European (non-Finnish) in 6 of 129130 chromosomes (freq: 0.000046), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish) and South Asian populations. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Met362 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |