Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001389323 | SCV001590646 | pathogenic | Congenital adrenal hypoplasia, X-linked; 46,XY sex reversal 2 | 2020-07-21 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with congenital adrenal hypoplasia (PMID: 19672728). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NR0B1 are known to be pathogenic (PMID: 7990958, 15841486). 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. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln76*) in the NR0B1 gene. It is expected to result in an absent or disrupted protein product. |