Genome and transcriptome sequencing reveal pathogenic activation of a pseudoexon in PKD1 via a de novo–common variant complex allele

Despite improvements in and access to clinical genetic testing, many patients with classic phenotypes remain without a molecular diagnosis. Such cases may reflect variants in noncoding regions or complex alleles made up of disparate sequence variants. In this article, we report a patient with autosomal dominant polycystic kidney disease caused by a deep intronic de novo single-nucleotide substitution forming a dinucleotide variant, with an adjacent common single-nucleotide variant (formerly single-nucleotide polymorphism) inherited from an unaffected parent.