ClinVar Miner

Submissions for variant NM_000275.3(OCA2):c.1580T>G (p.Leu527Arg)

dbSNP: rs779850564
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001366949 SCV001563274 uncertain significance not provided 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 527 of the OCA2 protein (p.Leu527Arg). This variant is present in population databases (rs779850564, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 22734612, 23010199). ClinVar contains an entry for this variant (Variation ID: 1057881). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt OCA2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genetic Services Laboratory, University of Chicago RCV001366949 SCV002066934 likely pathogenic not provided 2017-12-08 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003389336 SCV004101477 likely pathogenic Tyrosinase-positive oculocutaneous albinism criteria provided, single submitter clinical testing The missense variant c.1580T>G (p.Leu527Arg) has been observed in individual(s) with clinical features of oculocutaneous albinism (Jaworek et al. 2012, Mondal et al. 2012). This variant has been reported to the ClinVar database as Uncertain Significance. The p.Leu527Arg variant is novel (not in any individuals) in 1000 Genomes and is present in the gnomAD database with a frequency of 0.0004%. The amino acid Leu at position 527 is changed to a Arg 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. The residue is conserved across species. The amino acid change p.Leu527Arg in OCA2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Since the variant is in trans with the above described Pathogenic variant, it has been classified as Likely Pathogenic according to ACMG guidelines. This variant was observed in heterozygous state in her mother.
Baylor Genetics RCV003462930 SCV004208985 likely pathogenic SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2023-10-10 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005005212 SCV005630569 likely pathogenic Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2024-05-08 criteria provided, single submitter clinical testing

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