Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000382319 | SCV000330607 | pathogenic | not provided | 2016-06-23 | criteria provided, single submitter | clinical testing | The Q263X pathogenic variant in the HDAC8 gene has 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 Q263X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret Q263X as a pathogenic variant |
Equipe Genetique des Anomalies du Developpement, |
RCV000677735 | SCV000803892 | pathogenic | Cornelia de Lange syndrome 5 | 2017-10-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000677735 | SCV002166675 | pathogenic | Cornelia de Lange syndrome 5 | 2020-12-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with HDAC8-related conditions. ClinVar contains an entry for this variant (Variation ID: 280671). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln263*) in the HDAC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HDAC8 are known to be pathogenic (PMID: 19605684, 22885700, 24403048, 25075551, 26671848). |