Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Serv. |
RCV003485019 | SCV004231907 | pathogenic | Immunodeficiency 47 | 2024-01-19 | criteria provided, single submitter | clinical testing | The c.289-289G>A variant in ATP6AP1 had not been previously reported and was absent from large population studies. It was identified in a male patient exhibiting glycosylation deficiency with a type II plasma transferrin glycoform profile. RNA-seq analysis in fibroblasts revealed underespression and aberrant splicing of ATP6AP1. Subsequent studies in cDNA confirmed these findings and identified the intronic variant c.289-289G>A, located in a cryptic exon that was activated in this patient. The observed alterations at the RNA level were similar to those previously identified for the variant c.289-233C>T in another patient with glycosylation deficiency. Functional assays expressing the c.289-289G>A variant in HAP1 cells demonstrated the pathogenic impact of this variant by replicating the patient’s observed splicing alterations. Segregation of the variant in the family indicated it was de novo. In summary, the c.289-289G>A variant meets ACMG/AMP criteria to be classified as pathogenic based upon its absence from controls, a confirmed de novo variant consistent with patient’s phenotype, and functional evidence. |
| OMIM | RCV003485019 | SCV005090960 | pathogenic | Immunodeficiency 47 | 2024-07-29 | no assertion criteria provided | literature only |