Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003557842 | SCV004297182 | pathogenic | not provided | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 831 of the OCA2 protein (p.Ala831Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 21458243, 34838614). 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 not expected to disrupt OCA2 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690434 | SCV005184360 | likely pathogenic | Oculocutaneous albinism | 2024-05-01 | criteria provided, single submitter | clinical testing | Variant summary: OCA2 c.2491G>C (p.Ala831Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251106 control chromosomes (gnomAD v2.1). c.2491G>C has been reported in the literature in at least 4 compound heterozygous individuals affected with Oculocutaneous Albinism, who carried a second (likely) pathogenic variant (Wei_2011, Wei_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21458243, 34838614). ClinVar contains an entry for this variant (Variation ID: 2736158). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005003669 | SCV005630539 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2024-05-02 | criteria provided, single submitter | clinical testing |