Penetrance, effect and causal attribution: which number should be reported for recurrent copy-number variants?

Penetrance has a conventional and clinically useful meaning: among carriers of a genetic variant, what proportion manifest a specified phenotype? Goh et al. have identified a genuine problem in recurrent copy-number variant (CNV) counselling: historical estimates may be distorted by the assumed background prevalence of intellectual disability, ascertainment and clinically enriched cohorts. Their revised analysis of 83 recurrent CNVs is therefore an important corrective [ 1 , 2 , 3 ].