Re-evaluation and re-analysis of 152 research exomes five years after the initial report reveals clinically relevant changes in 18.

ABSTRACT: Iterative re-analysis of NGS results is not well investigated for published research cohorts of rare diseases. We revisited a cohort of 152 consanguineous families with developmental disorders (NDD) reported five years ago. We re-evaluated all reported variants according to diagnostic classification guidelines or our candidate gene scoring system (AutoCaSc) and systematically scored the validity of gene-disease associations (GDA). Sequencing data was re-processed using an up-to-date pipeline for case-level re-analysis. In 28/152 (18%) families, we identified a clinically relevant change. Ten previously reported (likely) pathogenic variants were re-classified as VUS/benign. In one case, the GDA (TSEN15) validity was judged as limited, and in five cases GDAs are meanwhile established. We ide

SUBMITTER: Bartolomaeus T 

PROVIDER: S-EPMC10545662 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature