Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000193262 | SCV000248364 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism | 2015-02-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000413048 | SCV000491125 | likely pathogenic | not provided | 2023-07-27 | criteria provided, single submitter | clinical testing | Observed as a single heterozygous variant or with a variant of uncertain significance, phase unknown, in patients with oculocutaneous albinism in published literature (Gronskov et al., 2009, Simeonov et al., 2013; Rimoldi et al., 2014); 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: 23824587, 33144682, 24361966, 28266639, 23504663, 27734839, 36116698, 7762554, 34838614, 29345414, 19060277) |
Genome- |
RCV000193262 | SCV002039992 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000413048 | SCV002133653 | pathogenic | not provided | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 404 of the OCA2 protein (p.Thr404Met). This variant is present in population databases (rs144812594, gnomAD 0.07%). This missense change has been observed in individual(s) with ocular albinism (PMID: 23504663, 24361966, 27734839). 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: 211766). 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. |
3billion | RCV000193262 | SCV002521137 | likely pathogenic | Tyrosinase-positive oculocutaneous albinism | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.008%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.96; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000211766). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
Centre for Human Genetics, |
RCV000193262 | SCV002558852 | pathogenic | Tyrosinase-positive oculocutaneous albinism | 2022-08-06 | criteria provided, single submitter | clinical testing | This missense variant replaces a conserved Threonine residue with a Methionine. This change is predicted damaging by the vast majority of prediction algorithms. This variant is very rare with no homozygous in gnomAD (AF: 0.0000636), was submitted to ClinVar by multiple submitters mostly classifying this variant as pathogenic/Likely pathogenic (VCV000211766.10), and is mentioned in at least three publications (PMID: 29345414‚ PMID: 10649493). Previous ClinVar submissions contain information regarding functional analysis demonstrating the pathogenic role of this variant. We identified this variant in a heterozygous state in one patient with Tyrosinase-positive oculocutaneous albinism in the Democratic Republic of Congo (DRC). This patient was heterozygous for the classic 2.7 deletion in the OCA2 gene. segregation analysis showed that the variant was in trans to the deletion in our patient. This variant was classified as pathogenic according to the ACMG guidelines |
Prevention |
RCV003401054 | SCV004109991 | pathogenic | OCA2-related condition | 2023-02-28 | criteria provided, single submitter | clinical testing | The OCA2 c.1211C>T variant is predicted to result in the amino acid substitution p.Thr404Met. This variant has been reported in the compound heterozygous and homozygous states in individuals with oculocutaneous albinism (OCA) (Rimoldi et al. 2014. PubMed ID: 24361966; Shahzad et al. 2017. PubMed ID: 28266639). This variant has also been reported in a patient with OCA, but a second causative variant was not found (Grønskov et al. 2009. PubMed ID: 19060277, Table 3). At PreventionGenetics, this variant along with a second pathogenic variant has been found in several affected individuals. This variant is classified as likely pathogenic by several independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/211766/). Given the evidence, we classify c.1211C>T (p.Thr404Met) as pathogenic. |
Baylor Genetics | RCV003462301 | SCV004208981 | pathogenic | SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2023-10-14 | criteria provided, single submitter | clinical testing | |
University of Washington Center for Mendelian Genomics, |
RCV000755087 | SCV000882905 | likely pathogenic | Nonsyndromic Oculocutaneous Albinism | 2017-03-07 | no assertion criteria provided | research |