ClinVar Miner

Submissions for variant NM_000275.3(OCA2):c.2201T>G (p.Leu734Arg)

gnomAD frequency: 0.00001  dbSNP: rs768934658
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779152 SCV000915663 likely pathogenic Tyrosinase-positive oculocutaneous albinism 2024-11-22 criteria provided, single submitter clinical testing The OCA2 c.2201T>G (p.Leu734Arg) missense variant has been was identified in trans with a pathogenic variant in individuals with a phenotype consistent with tyrosinase-positive oculocutaneous albinism (PMID:2310311). This variant is not observed at a significant frequency in version 4.0.0 of the Genome Aggregation Database. Multiple lines of computational evidence suggest the variant may impact the gene or gene product. This variant has been classified as likely pathogenic or pathogenic by multiple submitters in ClinVar. Based on the available evidence the c.2201T>G (p.Leu734Arg) variant is classified as likely pathogenic for tyrosinase-positive oculocutaneous albinism.
GeneDx RCV001568483 SCV001792363 likely pathogenic not provided 2023-09-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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: 23103111, 32966289)
Genome-Nilou Lab RCV000779152 SCV002041041 likely pathogenic Tyrosinase-positive oculocutaneous albinism 2021-11-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001568483 SCV002277916 pathogenic not provided 2024-04-03 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 734 of the OCA2 protein (p.Leu734Arg). This variant is present in population databases (rs768934658, gnomAD 0.0009%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 23103111; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 632225). 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.Leu734 amino acid residue in OCA2. Other variant(s) that disrupt this residue have been observed in individuals with OCA2-related conditions (PMID: 29345414), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005004413 SCV005630553 likely pathogenic Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2023-12-29 criteria provided, single submitter clinical testing

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