Genet Med. 2023 Oct 20:101006. doi: 10.1016/j.gim.2023.101006. Online ahead of print.
PURPOSE: Copy number variants (CNVs) and other non-SNV/indel variant types contribute an important proportion of diagnoses in individuals with suspected genetic disease. This study describes the range of such variants detected by genome sequencing (GS).
METHODS: For a pediatric cohort of 1032 participants undergoing clinical GS, we characterize the CNVs and other non-SNV/indel variant types that were reported, including aneuploidies, mobile element insertions, and uniparental disomies, and we describe the bioinformatic pipeline used to detect these variants.
RESULTS: Together, these genetic alterations accounted for 15.8% of reported variants. Notably, 67.9% of these were deletions, 32.9% of which overlapped a single gene, and many deletions were reported together with a second variant in the same gene in cases of recessive disease. A retrospective medical record review in a subset of this cohort revealed that up to six additional genetic tests were ordered in 68% (26/38) of cases, some of which failed to report the CNVs/rare variants reported on GS.
CONCLUSION: GS detected a broad range of reported variant types, including CNVs ranging in size from 1 Kb to 46 Mb.