Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Clinical Services Laboratory, |
RCV000390391 | SCV000358728 | likely benign | Distal spinal muscular atrophy, autosomal recessive 4 | 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 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 |
RCV000522669 | SCV000619856 | uncertain significance | not provided | 2017-08-11 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PLEKHG5 gene. The c.2485 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D829Y variant is observed in 26/6964 (0.4%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.2485 G>T may increase the strength of the cryptic splice acceptor site in exon 20. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If c.2485 G>T does not alter splicing, it will result in the D829Y missense change, which is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Aspartic Acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001083084 | SCV001098336 | likely benign | Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c | 2019-12-31 | criteria provided, single submitter | clinical testing |