Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001051643 | SCV001215810 | pathogenic | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 847988). This variant has not been reported in the literature in individuals affected with CYP11B2-related conditions. This variant is present in population databases (rs63748989, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Asn47*) in the CYP11B2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP11B2 are known to be pathogenic (PMID: 20494601, 22801770, 26936515). |
| Laboratory for Molecular Medicine, |
RCV001195423 | SCV001365774 | likely pathogenic | Corticosterone 18-monooxygenase deficiency | 2020-01-15 | criteria provided, single submitter | clinical testing | The p.Asn47X variant in CYP11B2 has not been previously reported in individuals with Corticosterone methyloxidase deficiency but has been identified in 0.002% (2/113716) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is a deletion of 10 nucleotides that leads to a premature termination codon at position 47, which is predicted to lead to a truncated or absent protein. Loss of function of the CYP11B2 gene is an established disease mechanism in autosomal recessive Corticosterone methyloxidase deficiency. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Corticosterone methyloxidase deficiency. ACMG/AMP Criteria applied: PVS1, PM2. |