ClinVar Miner

Submissions for variant NM_000275.3(OCA2):c.2158C>T (p.Arg720Cys)

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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 RCV003041213 SCV003442805 pathogenic not provided 2024-06-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 720 of the OCA2 protein (p.Arg720Cys). This variant is present in population databases (rs141545475, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 27734839; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2137627). 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.
Baylor Genetics RCV004572732 SCV005053783 likely pathogenic SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2024-02-06 criteria provided, single submitter clinical testing
GeneDx RCV003041213 SCV005384037 likely pathogenic not provided 2024-04-18 criteria provided, single submitter clinical testing 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: 31233279, 34838614, 27734839, 10987646, 23824587)
Fulgent Genetics, Fulgent Genetics RCV005002929 SCV005630555 likely pathogenic Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2024-06-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004744541 SCV005357952 pathogenic OCA2-related disorder 2024-06-10 no assertion criteria provided clinical testing The OCA2 c.2158C>T variant is predicted to result in the amino acid substitution p.Arg720Cys. This variant has been reported along with a second OCA2 variant in individuals with oculocutaneous albinism (Mauri et al. 2017. PubMed ID: 27734839; Table S1, Wei et al. 2022. PubMed ID: 34838614). This variant has also been reported in the heterozygous state in a family with susceptibility to cutaneous melanoma (Nathan et al. 2019. PubMed ID: 31233279). An alternate substitution of this amino acid residue (p.Arg720Pro) has been reported along with a second OCA2 variant in an individual with oculocutaneous albinism (Ma et al. 2021. PubMed ID: 34707637). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. Given the evidence, we interpret this variant as pathogenic.

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