Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002472073 | SCV002768460 | pathogenic | 46,XY sex reversal 3 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with adrenocortical insufficiency, (MIM#612964), 46, XX sex reversal 4, (MIM# 617480), 46XY sex reversal 3, (MIM#612965), premature ovarian failure 7, (MIM#612964) and spermatogenic failure 8, (MIM#613957). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance. Unaffected carriers have been reported in a number of families (PMID: 31513305). (I) 0115 - Variants in this gene are known to have variable expressivity. Intra-familial variability have been reported with the same variant resulting in different phenotypes (PMID: 31513305). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. At least 10 other NMD-predicted variants have been reported in patients with NR5A1-related disorders (PMID: 31513305). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |