Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519531 | SCV000620822 | pathogenic | not provided | 2023-05-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD) |
| Labcorp Genetics |
RCV001853675 | SCV002178282 | uncertain significance | Combined oxidative phosphorylation defect type 17 | 2022-07-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu482*) in the ELAC2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ELAC2 cause disease. This variant is present in population databases (rs763770476, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ELAC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 452048). 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. |
| Ambry Genetics | RCV002528261 | SCV003547677 | pathogenic | Inborn genetic diseases | 2022-03-24 | criteria provided, single submitter | clinical testing | The c.1444G>T (p.E482*) alteration, located in exon 16 (coding exon 16) of the ELAC2 gene, consists of a G to T substitution at nucleotide position 1444. This changes the amino acid from a glutamic acid (E) to a stop codon at amino acid position 482. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of <0.01% (9/282878) total alleles studied. The highest observed frequency was 0.01% (9/129180) of European (non-Finnish) alleles. Based on the available evidence, this alteration is classified as pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001853675 | SCV003928483 | likely pathogenic | Combined oxidative phosphorylation defect type 17 | 2023-04-19 | criteria provided, single submitter | clinical testing | Variant summary: ELAC2 c.1444G>T (p.Glu482X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.2e-05 in 251470 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1444G>T in individuals affected with Combined Oxidative Phosphorylation Defect Type 17 and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as either pathogenic (n=2) or VUS (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |