Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001037044 | SCV001200437 | likely pathogenic | Reticular dysgenesis | 2019-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with proline at codon 175 of the AK2 protein (p.Arg175Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of severe combined immunodeficiency (PMID: 23763981, 29713328). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg175 amino acid residue in AK2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23014587, 30697212). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Center for Genomic Medicine, |
RCV001037044 | SCV003924313 | likely pathogenic | Reticular dysgenesis | 2023-05-08 | criteria provided, single submitter | research |