Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000372032 | SCV000465747 | uncertain significance | Pontocerebellar hypoplasia type 6 | 2018-01-13 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Genetic Services Laboratory, |
RCV000501102 | SCV000596720 | uncertain significance | not specified | 2017-04-19 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001723960 | SCV002520081 | uncertain significance | not provided | 2022-05-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Victorian Clinical Genetics Services, |
RCV000372032 | SCV002768047 | uncertain significance | Pontocerebellar hypoplasia type 6 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_020320.4(RARS2):c.754T>A in exon 9 of 20 of the RARS2 gene. This substitution is predicted to create a major amino acid change from tyrosine to asparagine at position 252 of the protein, NP_064716.2(RARS2):p.(Tyr252Asn). The tyrosine at this position has very high conservation (100 vertebrates, UCSC), and is located within the tRNA synthetases class I (R) domain. In silico software predicts this variant to be pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at frequencies of 0.03% (38 heterozygotes, 0 homozygotes) in the non-Finnish European population and 0.02% (59 heterozygotes, 0 homozygotes) in the global population. It has been previously reported as a variant of uncertain significance (VUS) in clinical cases (ClinVar). Based on information available at the time of curation, this variant has been classified as a VUS with POTENTIAL CLINICAL RELEVANCE. |
Labcorp Genetics |
RCV001723960 | SCV003247505 | uncertain significance | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 252 of the RARS2 protein (p.Tyr252Asn). This variant is present in population databases (rs140692271, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with RARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 358236). 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 RARS2 protein function. 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. |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001723960 | SCV001953156 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001723960 | SCV001966196 | uncertain significance | not provided | no assertion criteria provided | clinical testing |