AAVC: an automated framework for high-accuracy ACMG-based variant classification.

Automated ACMG/ClinGen classification leveraging large public databases and in silico predictors.

AAVC is a new tool for automated variant classification following ACMG standards and ClinGen specifications, leveraging large public databases and in silico predictors. It reaches 94.39 % concordance with FDA-recognised classifications, outperforming existing tools, and reclassifies 55 % of ClinVar VUS into clinically significant categories. Applied to the Turkish Variome, it identified 215 pathogenic, likely pathogenic or VUS-high variants in secondary-finding genes, revealing that one in ten individuals carries an actionable genotype. The tool is freely available online for laboratories and research groups.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

In an already crowded field of automated ACMG tools, AAVC stands out for its high concordance with FDA classifications and a notable ability to resolve VUS — the central challenge of exome/genome diagnostics being no longer variant capture but interpretation. The one-in-ten rate of actionable genotypes illustrates the potential impact on secondary findings. It needs validation on prospective diagnostic cohorts beyond the Turkish context.

Analysis by Dr Thibaut Benquey