ClinVar Miner

Submissions for variant NM_000275.3(OCA2):c.2359G>A (p.Ala787Thr)

gnomAD frequency: 0.00006  dbSNP: rs142988897
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Total submissions: 7
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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, 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, CHU Bordeaux RCV000989277 SCV003804563 likely pathogenic Tyrosinase-positive oculocutaneous albinism criteria provided, single submitter clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine 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, King Faisal Specialist Hospital and Research Center RCV003489991 SCV004232534 uncertain significance not specified 2024-01-18 criteria provided, single submitter research

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