P750: Cytogenetic profiles of clinically diagnosed Down syndrome (DS) cohort reported at a single centered accredited laboratory in Sri Lanka

disease specific threshold approach, an overall reduction of 4.34% (136/3134) in VUS rates was observed for BS1/BA1 eligible downgrades within the stated time window.This contrasts with a generalized approach, where no decrease in VUS rates was observed (0/3134) within the same time window.The reduction in VUS rates achieved using the 7 gene-disease specific thresholds impacted 12,073 individuals, either by a VUS being downgraded or a variant not being reported as it was classified as likely benign or benign.Conclusion: Here we show that the application of BS1/BA1 evidence, when calculated as a function of the known disease-specific architecture, decreases the rate of VUS in clinically relevant genes compared to a generalized approach.This reduction in VUS impacts many individuals, reducing the burden associated with receiving an uncertain test result.