# ACMG-Recommended Actionable Secondary Findings from 1600 Clinical Exomes in the South Marmara Region in Turkiye

## TL;DR

This study examines ACMG-recommended secondary genetic findings in 1600 individuals from Turkiye, revealing new variants and highlighting the need for tailored reporting guidelines.

## Contribution

The study identifies novel variants and emphasizes the need for population-specific ACMG secondary findings guidelines in high-consanguinity regions.

## Key findings

- SF variants reported in ClinVar were found in 5.375% of the 1600 individuals.
- 212 different variants in 226 individuals were identified that were not reported in ClinVar.
- The study highlights variability in findings due to differences in participant characteristics and sequencing methods.

## Abstract

In genetic disease assessment centers, DNA sequencing can produce results irrelevant to the genetic examination’s purpose. The American College of Medical Genetics and Genomics (ACMG) recommends evaluating and reporting 81 genes discovered using clinical genomic sequencing. While population studies on large cohorts can provide statistics on the prevalence of secondary findings (SFs), no studies have been published yet on large cohorts in Turkiye. We investigated ACMG SF by evaluating clinical exome sequencing data in 1600 individuals from different regions in Turkiye. We detected SF variants reported in ClinVar in 86 individuals (5.375%). Of the SFs, 30% were cardiovascular, 26% were cancer, 16% were neonatal metabolic disorders, and 28% were variants associated with various genetic diseases. In addition, we identified 212 different variants in 226 individuals and 45 different genes, which were not reported in ClinVar. When our results are compared with the Turkish National Genome and Bioinformatics Project database and studies in the literature, the studies vary in terms of participant characteristics, sequencing techniques, and versions of the ACMG SF list. Our findings highlight the importance of expanding and tailoring SF reporting guidelines in populations with high consanguinity and limited cohort-based data.