Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001851652 | SCV002237363 | likely pathogenic | not provided | 2023-09-25 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Ala486 amino acid residue in SLC45A2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27706749, 32552135). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 486 of the SLC45A2 protein (p.Ala486Val). This variant is present in population databases (rs121912620, gnomAD 0.002%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 14722913). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 4502). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC45A2 protein function. 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. |
| OMIM | RCV000004760 | SCV000024936 | pathogenic | Oculocutaneous albinism type 4 | 2004-02-01 | no assertion criteria provided | literature only |