Fig. 3: Baseline copy-number variants (CNVs) unrelated to clinical phenotype in a large cohort.

The clinical significance of these CNVs was not evaluated beyond their being deletions in American College of Medical Genetics and Genomics–listed genes with known loss-of-function (LOF) mutational mechanisms. CNVs in genes that belonged to the same clinical specialty as those ordered for clinical testing were removed from the analysis. Single-exon low-quality calls were removed to reduce potential false-positive calls. a Histogram showing the number of distinct CNVs observed in genes analyzed for baseline CNVs. The columns in the chart show the number of times the CNVs were observed. The line graph shows the proportion of total observed CNVs in each frequency bin. For example, the first column shows that more than 1100 CNVs occurred just once and, in aggregate, accounted for roughly 25% of all CNVs. By contrast, the last column indicates that 36 CNVs were found more than 15 times and represented more than 40% of all baseline CNVs. b Histogram showing the number of genes that contained baseline CNVs. The columns in the chart show incremental increases in the number of CNVs observed in a gene. The line graph shows the proportion of CNVs at arbitrary increments of CNV occurrence per gene. For example, nearly 240 genes had just one CNV, and together these CNVs accounted for roughly 6% of all events. By contrast, approximately 45 genes had more than 15 CNVs each, which represented slightly more than 60% of all CNVs. c Distribution of baseline CNVs is shown according to the number of exons affected. Multiexon CNVs include three classes of 5′ terminal exons, internal exons, and 3′ terminal exons. (D and E) Burden of baseline CNVs in genes according to mode of inheritance and zygosity. CNVs in genes with LOF mutational mechanisms are shown in part (d) and those in genes without LOF mechanisms are shown in part (e). CNVs in X-linked (XL) genes were categorized as those observed as heterozygous events in females and hemizygous events in males. AD autosomal dominant, AR autosomal recessive, F female, M male, het heterozygous, hom homozygous