Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Research Center, |
RCV000626181 | SCV000746819 | uncertain significance | Infantile cerebellar-retinal degeneration | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001355735 | SCV002415444 | likely benign | not provided | 2024-12-05 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001355735 | SCV001550698 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The ACO2 p.Thr517Met variant was not identified in the literature but was identified in dbSNP (ID: rs540169523) and ClinVar (classified as uncertain significance by Genomic Research Center, Shahid Beheshti University of Medical Sciences). The variant was identified in control databases in 74 of 282884 chromosomes at a frequency of 0.0002616 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 71 of 30616 chromosomes (freq: 0.002319), Other in 2 of 7224 chromosomes (freq: 0.000277) and European (non-Finnish) in 1 of 129182 chromosomes (freq: 0.000008), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, or European (Finnish) populations. The p.Thr517 residue is not conserved in mammals and four out of five 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. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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. |