Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 <i>CHEK2</i> Splice-Site Variants

Abstract

Incorporation of minigene read-outs into an ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based classification scheme allowed us to classify 32 CHEK2 variants (27 pathogenic/likely pathogenic and 5 likely benign). However, 20 variants (38%) remained of uncertain significance, reflecting in part the complex splicing patterns of this gene.