We estimated c, the number of observed risk genes, as d minus the number of recurrent variants (11) plus the number of genes with recurrent variants (5). d is the total number of risk associated variants, so we subtracted the number of de novo variants present in recurrently mutated genes to account for the multiple variants in the same gene. We then added back the number of genes with recurrent variants to obtain the final estimate of c (essentially, we removed the extra variants within genes with multiple de novo variants). Therefore, c was equal to 54 − 11 + 5 = 48.
