Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001068920 | SCV001234056 | pathogenic | DICER1-related tumor predisposition | 2020-06-17 | criteria provided, single submitter | clinical testing | This variant disrupts the entire double strand RNA binding domain (dsRBD) of the DICER1 protein, which has been shown to affect enzyme activity, substrate RNA binding, and nuclear localization of the DICER1 protein (PMID: 23882114,15242644, 18508075, 23272173). While functional studies have not been performed to directly test the effect of this variant on DICER1 protein function, this suggests that disruption of this region of the protein is causative of disease. This sequence change results in a premature translational stop signal in the DICER1 gene (p.Ser1823Valfs*34). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 100 amino acids of the DICER1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Sertoli-Leydig cell tumor of the ovary (Invitae). ClinVar contains an entry for this variant (Variation ID: 862236). For these reasons, this variant has been classified as Pathogenic. |