Practically, these data serve as a clinical resource useful in diagnostics (Tables 1 and 2). The large number of controls and cases provides estimates of penetrance for 60 pathogenic CNVs (accounting for ~10% of cases) and sheds light on either ambiguous or previously unknown pathogenic variants, including 14 novel or previously marginally supported CNV loci that collectively represent ~0.7% (112 of 15,767, Table 2 and Supplementary Note) of the individuals studied here. We note that while one CNV-locus (10p15.3 duplications) appeared to be enriched among cases as a result of ancestry differences between cases and controls, the aggregate ethnic composition of the 14 loci in Table 2 matched closely our control dataset (see Supplementary Note, Supplementary Figures 10 and 11), suggesting that population stratification for rare variants is unlikely to explain the enrichment at these loci. The size distribution (median of 940 kb), inheritance rate (15 of 34 tested CNVs are de novo, with at least 1 de novo variant observed in 6 of the 14 loci), and overlap with DECIPHER entries further support the disease risk for these CNV-loci.
