ClinVar Miner

Submissions for variant NM_000275.3(OCA2):c.593C>T (p.Pro198Leu)

gnomAD frequency: 0.00031  dbSNP: rs183487020
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000604129 SCV000731693 likely pathogenic Tyrosinase-positive oculocutaneous albinism 2017-06-27 criteria provided, single submitter clinical testing The p.Pro198Leu (NM_000275.2 c.593C>T) variant in OCA2 has been reported in at l east 1 homozygous, 2 compound heterozygous and 1 heterozygous individuals of Tur kish, Chinese and Japanese ancestry with oculocutaneous albinism II (Rooryck 200 8, Suzuki 2003, Wang 2015, and Wei 2010). This variant has also been reported in ClinVar (Variation ID# 198063). This variant has been identified in 0.12% (13/1 0222) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://e xac.broadinstitute.org; dbSNP rs183487020). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a r ecessive carrier frequency. Computational prediction tools and conservation anal ysis suggest that the p.Pro198Leu variant may impact the protein, though this in formation is not predictive enough to determine pathogenicity. In summary, altho ugh additional studies are required to fully establish its clinical significance , the p.Pro198Leu variant is likely pathogenic based upon its biallelic observat ions in multiple affected individuals and low population frequency.
Labcorp Genetics (formerly Invitae), Labcorp RCV000179280 SCV001041824 pathogenic not provided 2024-10-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 198 of the OCA2 protein (p.Pro198Leu). This variant is present in population databases (rs183487020, gnomAD 0.1%). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 19865097, 25919014, 29437493; internal data). ClinVar contains an entry for this variant (Variation ID: 198063). 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 not expected to disrupt OCA2 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000179280 SCV001793614 pathogenic not provided 2024-03-29 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: 32552135, 22995991, 12713581, 30609409, 25919014, 19865097, 18821858, 24118800, 31196117, 34838614)
CeGaT Center for Human Genetics Tuebingen RCV000179280 SCV001961480 uncertain significance not provided 2021-08-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000604129 SCV002040103 likely pathogenic Tyrosinase-positive oculocutaneous albinism 2021-11-07 criteria provided, single submitter clinical testing
3billion, Medical Genetics RCV000604129 SCV002059145 likely pathogenic Tyrosinase-positive oculocutaneous albinism 2022-01-03 criteria provided, single submitter clinical testing Same nucleotide change resulting in same amino acid change has been previously reported to be associated with OCA2 related disorder (ClinVar ID: VCV000198063, PMID:12713581, PS1_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88, PP3_P). A missense variant is a common mechanism associated with Albinism (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000124, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV003468869 SCV004208990 pathogenic SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2024-03-28 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005003533 SCV005630601 pathogenic Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES 2024-04-29 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000179280 SCV000231505 uncertain significance not provided 2015-01-20 flagged submission clinical testing

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