Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000760846 | SCV000890742 | pathogenic | not provided | 2018-12-03 | criteria provided, single submitter | clinical testing | The R488X variant in the DOCK6 gene has been not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R488X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R488X as a pathogenic variant. |
Labcorp Genetics |
RCV000760846 | SCV002166887 | pathogenic | not provided | 2021-05-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg488*) in the DOCK6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DOCK6 are known to be pathogenic (PMID: 21820096, 25824905). This variant is present in population databases (rs369389970, ExAC 0.01%). This variant has not been reported in the literature in individuals with DOCK6-related conditions. ClinVar contains an entry for this variant (Variation ID: 620465). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |