Exploring and Expanding Secondary Findings Through Exome Sequencing in the Turkish Population

AKCAN M. B., CEYLAN KÖSE C., Müge Çelik K., TEKİN K., Kaya D., SILAN F.

Annals of Human Genetics, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1111/ahg.12592
  • Dergi Adı: Annals of Human Genetics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, International Bibliography of Social Sciences, BIOSIS, CAB Abstracts, EMBASE, zbMATH
  • Anahtar Kelimeler: ACMG, cancer, cardiovascular disease, exome sequencing, secondary findings
  • Çanakkale Onsekiz Mart Üniversitesi Adresli: Evet

Özet

Introduction: Exome-sequencing (ES) methods enable accurate diagnosis in challenging cases and uncover secondary findings (SFs) potentially linked to life-threatening or preventable diseases. The American College of Medical Genetics and Genomics (ACMG) publishes a list detailing which SFs should be reported and regularly updates it. We aimed to compare results across different SF versions in patients and explore additional SFs to identify potential new recommendations for SF reporting. Methods: We conducted a retrospective analysis of 724 patients to identify ACMG SFs using the QIAGEN Clinical Insight (QCI) Interpret database. Furthermore, we investigated pathogenic/likely pathogenic variants in cancer and cardiovascular disease genes not listed in ACMG SFs, as well as genes associated with common diseases prevalent in our country. Methods: ACMG SF v3.2 variants were identified in 56 patients (7.7%), with no observed differences between ACMG v3.1 and v3.2. Additionally, our analysis revealed that 208 patients harbored non-ACMG SF variants. Conclusion: In this study, we focused on known SFs and identified additional variants that could be considered as new recommendations. While expanding the list of SFs can pose challenges during analyses and genetic counseling, a thoughtfully curated SF list has the potential to enhance patient care and improve clinical outcomes.