Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000989277 | SCV001139533 | pathogenic | Tyrosinase-positive oculocutaneous albinism | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001869361 | SCV002243281 | pathogenic | not provided | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 787 of the OCA2 protein (p.Ala787Thr). This variant is present in population databases (rs142988897, gnomAD 0.01%). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 17160937, 20426782, 25455140). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 803060). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on OCA2 protein function. This variant disrupts the p.Ala787 amino acid residue in OCA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20861488, 23744323, 26165494). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV002497282 | SCV002809917 | pathogenic | Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2021-12-20 | criteria provided, single submitter | clinical testing | |
Laboratoire de Génétique Moléculaire, |
RCV000989277 | SCV003804563 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism | criteria provided, single submitter | clinical testing | ||
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000989277 | SCV004048191 | pathogenic | Tyrosinase-positive oculocutaneous albinism | criteria provided, single submitter | clinical testing | "The OCA2 (c.2359G>A) (p.Ala787Thr) variant has been reported in homozygous state in individuals affected with Oculocutaneous albinism in Indian populations. Haplotype analysis revealed p. Ala787Thr mutation as a founder mutation (M. Sengupta et. al. 2010). The allele frequency (0.004374%) in the gnomAD and novel in 1000 genome database. The amino acid change p.Ala787Thr in OCA2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ala at position 787 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. For these reasons, this variant has been classified as Pathogenic. | |
Baylor Genetics | RCV003461297 | SCV004209003 | pathogenic | SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2023-09-09 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV003489991 | SCV004232534 | uncertain significance | not specified | 2024-01-18 | criteria provided, single submitter | research |