Clinical genomic sequencing can identify pathogenic variants unrelated to the 
initial clinical question, but of medical relevance to the patients and their 
families. With ongoing discussions on the utility of disclosing or searching for 
such variants, it is of crucial importance to obtain unbiased insight in the 
prevalence of these incidental or secondary findings, in order to better weigh 
potential risks and benefits. Previous studies have reported a broad range of 
secondary findings ranging from 1 to 9%, merely attributable to differences in 
study design, cohorts tested, sequence technology used and genes analyzed. Here, 
we analyzed WES data of 1640 anonymized healthy Dutch individuals to establish 
the frequency of medically actionable disease alleles in an outbred population 
of European descent. Our study shows that 1 in 38 healthy individuals (2.7%) has 
a (likely) pathogenic variant in one of 59 medically actionable dominant disease 
genes for which the American College of Medical Genetics and Genomics (ACMG) 
recommends disclosure. Additionally, we identified 36 individuals (2.2%) to be a 
carrier of a recessive pathogenic disease allele. Whereas these frequencies of 
secondary findings are in line with what has been reported in the East-Asian 
population, the pathogenic variants are differently distributed across the 59 
ACMG genes. Our results contribute to the debate on genetic risk factor 
screening in healthy individuals and the discussion whether the potential 
benefits of this knowledge and related preventive options, outweigh the risk of 
the emotional impact of the test result and possible stigmatization.