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In this study, we aimed to re\u2010classify variants of uncertain significance (VUS) in OCA2 by evaluating subcellular localization and channel activity through multiplex assays of variant effect (MAVEs). Following the ClinGen guidelines for PS3 evidence, we selected 13 <jats:italic>OCA2<\/jats:italic> variants from ClinVar (6 benign\/likely benign [B\/LB] and 7 pathogenic\/likely pathogenic [P\/LP]) for OddsPath analysis. The P\/LP variants exhibited abnormal functions, while the B\/LB variants demonstrated normal functions, supporting the application of \u201cPS3_moderate\u201d evidence for VUS re\u2010classification. In our functional evaluation of 30 VUS identified in 38 individuals with suspected OCA\u20102 by trio whole\u2010exome sequencing, we observed 6 VUS with abnormal localization and 11 with abnormal channel activity. Based on PS3_moderate evidence, 8 VUS were re\u2010classified as LP, while 22 remained VUS. Consequently, 7 out of 38 previously undiagnosed patients received a molecular diagnosis of OCA\u20102. These MAVEs offer a robust approach for curating <jats:italic>OCA2<\/jats:italic> VUS, enhancing diagnostic accuracy, and informing genetic counseling. Additionally, this variant cohort is a valuable resource for public databases.<\/jats:p>","DOI":"10.1111\/pcmr.13212","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T11:29:46Z","timestamp":1733398186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Curation of <i>OCA2<\/i> Variants of Uncertain Significance From Chinese Oculocutaneous Albinism Patients Based on Multiplex Assays"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5415-9593","authenticated-orcid":false,"given":"Qingsong","family":"Yang","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Genetics and Birth Defects Control Center, National Center for Children's Health, MOE Key Laboratory of Major Diseases in Children Beijing Children's Hospital, Capital Medical University  Beijing 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