Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230923 | SCV003929033 | pathogenic | Congenital adrenal hyperplasia | 2024-09-12 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the deletion of exons 4-7 in the CYP21A2 gene. A presumed nomenclature of c.(447+1_448-1)_(939+1_940-1)del has been designated for the purposes of this classification. It is assumed to be a tandem duplication in direct orientation (PMIDs: 25640679, 30054569). This Copy Number Variant (CNV) is predicted to result in an in-frame deletion within this gene. No structural variants are annotated for the CYP21A2 gene in the in the gnomAD database SVs v2.1 and v4.1 datasets, likely due to possible pseudogene interference. Exon 4-7 deletions/conversions have been reported in the literature in affected individuals (e.g., Xia_2022). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, several missense variants and in-frame deletions have been reported within the deleted region as pathogenic by our lab and others in ClinVar and are cited in association with Adrenal hyperplasia in HGMD. No other submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. |