Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001332321 | SCV001524600 | uncertain significance | Pontocerebellar hypoplasia type 6 | 2020-07-09 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001586133 | SCV001821451 | uncertain significance | not specified | 2021-08-31 | criteria provided, single submitter | clinical testing | Variant summary: RARS2 c.536-5G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant weakens and one predicts the variant abolishes a 5' cryptic donor site. Two predict the variant abolishes/weakens a canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250006 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.536-5G>A in individuals affected with Pontocerebellar Hypoplasia, Type 6 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |