Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000520462 | SCV000621790 | likely pathogenic | not provided | 2017-10-19 | criteria provided, single submitter | clinical testing | The G359R variant in the OCA2 gene has been reported previously as homozygous in a family with oculocutaneous albinism (Shahzad et al., 2017). The G359R variant is not observed in large population cohorts (Lek et al., 2016). The G359R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G359R as a likely pathogenic variant. |
| Invitae | RCV000520462 | SCV002114736 | likely pathogenic | not provided | 2023-05-16 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Gly359 amino acid residue in OCA2. Other variant(s) that disrupt this residue have been observed in individuals with OCA2-related conditions (PMID: 27734839), which suggests that this may be a clinically significant amino acid residue. 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 OCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 452941). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 28266639; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 359 of the OCA2 protein (p.Gly359Arg). |
| University of Washington Center for Mendelian Genomics, |
RCV000755085 | SCV000882903 | likely pathogenic | Nonsyndromic Oculocutaneous Albinism | 2017-03-07 | no assertion criteria provided | research |