# Secondary Findings from Exome Sequencing of a Greek Cohort

## TL;DR

This study reports on the frequency of clinically significant genetic variants in a Greek population using exome sequencing, highlighting potential health risks unrelated to the initial reason for testing.

## Contribution

This is the first study to calculate the prevalence of pathogenic variants in ACMG actionable genes for secondary findings in Greece.

## Key findings

- 4.3% of individuals carried pathogenic or likely pathogenic variants in genes linked to dominant disorders.
- A pathogenic founder variant in BRCA1 and high prevalence of LDLR variants were identified in the Greek cohort.
- The study provides insights for national carrier screening programs and targeted treatment strategies.

## Abstract

Exome sequencing (ES) is an essential part in clinical diagnosis of hereditary disorders. However, ES can reveal secondary findings (SFs) in medically actionable genes that are not related to the patient’s phenotype. In this study, we performed ES to 280 unrelated individuals of a Greek cohort and calculated the frequency of SFs in 81 ACMG SF v3.2 genes. Variants were classified using the standards and guidelines established by the American College of Medical Genetics and Genomics (ACMG). We identified 12 individuals (4.3%) who carried a pathogenic (P)/likely pathogenic (LP) variant in genes associated with dominant disorders. The variants were found in genes BRCA1, BRCA2, MSH6, LDLR, MYH7, and TTN. Notably, we discovered a P founder variant for the Greek population and one P variant with high prevalence in BRCA1 gene. Additionally, we observed a high prevalence of P/LP variants in the LDLR gene. In conclusion, this is the first study that calculates the prevalence of P/LP variants in the ACMG actionable gene list for SFs in Greece. The results of our study could serve as a guide for the national carrier screening program and may contribute to the precise treatment of certain human disorders.