ClinVar Miner

Submissions for variant NM_000275.3(OCA2):c.1427A>G (p.Asn476Ser)

gnomAD frequency: 0.00001  dbSNP: rs763819379
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192364 SCV000248366 pathogenic Tyrosinase-positive oculocutaneous albinism 2015-02-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004689667 SCV005185482 likely pathogenic Oculocutaneous albinism 2024-05-29 criteria provided, single submitter clinical testing Variant summary: OCA2 c.1427A>G (p.Asn476Ser) results in a conservative amino acid change located in the Citrate transporter-like domain (IPR004680) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251488 control chromosomes (gnomAD). c.1427A>G has been reported in the literature in individuals affected with Oculocutaneous Albinism (Preising_2007, Mauri_2016, Lasseaux_2018). 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: 29345414, 27734839, 17960121). ClinVar contains an entry for this variant (Variation ID: 211767). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005008126 SCV005630575 likely pathogenic Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2024-05-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005089985 SCV005836403 pathogenic not provided 2024-05-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 476 of the OCA2 protein (p.Asn476Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of oculocutaneous albinism (PMID: 17960121, 27734839, 29345414). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 211767). 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%. This variant disrupts the p.Asn476 amino acid residue in OCA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17385796, 31077556, 32552135). 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.

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