Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493655 | SCV000582329 | likely pathogenic | not provided | 2023-02-21 | criteria provided, single submitter | clinical testing | Observed with a second OCA2 variant in an individual with clinical oculocutaneous albinism, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Ma L et al., 2021); Identified in two families with cutaneous malignant melanoma, including one individual who harbored a second OCA2 missense variant, but additional clinical information was not provided (Goldstein et al., 2017); Identified as a single heterozygous variant in a proband with features of oculocutaneous albinism (Marti et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32966289, 29036293, 34707637, 28976636) |
| Fulgent Genetics, |
RCV000762937 | SCV000893360 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000493655 | SCV002314095 | pathogenic | not provided | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 777 of the OCA2 protein (p.Cys777Tyr). This variant is present in population databases (rs776814755, gnomAD 0.01%). This missense change has been observed in individuals with clinical features of oculocutaneous albinism (PMID: 28976636; Invitae). ClinVar contains an entry for this variant (Variation ID: 429697). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Victorian Clinical Genetics Services, |
RCV002470881 | SCV002767262 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with brown oculocutaneous albinism and oculocutaneous, type II albinism (MIM#203200). (I) 0106 - This gene is associated with autosomal recessive disease. A single variant has been reported in two families with dominant oculocutaneous albinism (PMID: 32741191). (I) 0115 - Variants in this gene causing oculocutaneous albinism are known to have variable expressivity (PMID: 24518832). (I) 0200 - Variant is predicted to result in a missense amino acid change from cysteine to tyrosine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a condition (8 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated transmembrane helix within the permease P domain (NCBI). (I) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. An alternative change p.(Cys777Arg) has been reported in a heterozygous patient with albinism (PMID: 20861488). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported twice as likely pathogenic (ClinVar), and has been observed in a heterozygous patient with albinism (PMID: 28976636). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (LABID). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Laboratoire de Génétique Moléculaire, |
RCV002470881 | SCV003804559 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism | criteria provided, single submitter | clinical testing | ||
| Baylor Genetics | RCV003470613 | SCV004209015 | likely pathogenic | SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2023-08-14 | criteria provided, single submitter | clinical testing |