Burden of pathogenic variants in genes associated with medically actionable disease in the Slovenian population

The prevalence of pathogenic variants in disease-related genes is population-specific and is of vital importance for the development of national health policies. It is especially important with medically actionable diseases, where early interventions and preventive surveillance are available and can enable effective preventive measures or timely treatment.

We have examined the burden of pathogenic variants in 84 genes associated with medically actionable disease in exome sequencing data of 14.000 Slovenian individuals, representing 0.7% of the whole Slovenian population. The variants were classified according to the ACMG criteria, and the prevalence of pathogenic variants in each gene was compared to the burden of pathogenic variants in the gnomAD database.

The prevalence of pathogenic variants in 84 medically actionable genes in the Slovenian population is 2.73%. Furthermore, we identified an additional 0.48% of novel candidate likely pathogenic variants. Together, these variants accounted for 3.21% of all detected potentially medically actionable variants. Of this variation, 1.73% is cardio-related, 1.21% is cancer-related, and 0.27% is associated with other phenotypes. The prevalence of pathogenic variants in BRCA1, LDLR, and HFE differs significantly between the Slovenian population and the gnomAD database.

Revealing the prevalence of pathogenic variants in medically actionable genes in the Slovenian population highlights the need for careful interpretation of genomic data in our population, as approximately one in 31 individuals carries a potentially medically actionable variant. Our results advocate for population-specific evaluation of genetic disease burden, as tailored measures, particularly for genes enriched in a given population, may be warranted.