Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000179741 | SCV000232038 | uncertain significance | not provided | 2014-11-20 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001118260 | SCV001276530 | uncertain significance | Tyrosinase-positive oculocutaneous albinism | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Invitae | RCV000179741 | SCV001512658 | likely pathogenic | not provided | 2024-01-29 | 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 243 of the OCA2 protein (p.Arg243Cys). This variant is present in population databases (rs138065338, gnomAD 0.2%). This missense change has been observed in individual(s) with OCA2-related conditions (PMID: 19865097, 30835348, 34838614). ClinVar contains an entry for this variant (Variation ID: 198411). 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 not expected to disrupt OCA2 protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Genome- |
RCV001118260 | SCV002040520 | uncertain significance | Tyrosinase-positive oculocutaneous albinism | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002478597 | SCV002788147 | uncertain significance | Tyrosinase-positive oculocutaneous albinism; SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2022-04-18 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003468871 | SCV004208971 | likely pathogenic | SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES | 2023-10-27 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003955089 | SCV004776845 | uncertain significance | OCA2-related condition | 2024-02-07 | criteria provided, single submitter | clinical testing | The OCA2 c.727C>T variant is predicted to result in the amino acid substitution p.Arg243Cys. This variant has been reported along with a second OCA2 variant in individuals with oculocutaneous albinism (Wei et al. 2010. PubMed ID: 19865097; Wei et al. 2021. PubMed ID: 34838614). This variant is reported in 0.17% of alleles in individuals of East Asian descent in gnomAD, indicating it is relatively common in this population. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |