Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002320860 | SCV002610551 | pathogenic | Inborn genetic diseases | 2019-06-06 | criteria provided, single submitter | clinical testing | The c.3155+5G>A intronic pathogenic mutation results from a G to A substitution 5 nucleotides after coding exon 30 in the DEPDC5 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the available evidence, this variant is classified as a pathogenic mutation. |
| Labcorp Genetics |
RCV003594185 | SCV004249604 | uncertain significance | Familial focal epilepsy with variable foci | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 31 of the DEPDC5 gene. It does not directly change the encoded amino acid sequence of the DEPDC5 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1728228). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. |