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. 2025 May;89(2-3):67-76.
doi: 10.1111/ahg.12586. Epub 2024 Nov 15.

Secondary findings in 443 exome sequencing data

Marija Branković  1 , Heonjong Han  2 , Milena Janković  3 , Ana Marjanović  1 , Nikola Andrejic  1 , Ilija Gunjić  4 , Vanja Virić  1   3 , Aleksa Palibrk  1   3 , Hane Lee  2 , Stojan Peric  1   3
Affiliations

Secondary findings in 443 exome sequencing data

Marija Branković et al. Ann Hum Genet. 2025 May.

Abstract

Exome sequencing (ES) may identify and report secondary findings that are unrelated to the primary disease for which the patient underwent genetic testing, but are of potential value in patient care. In this study, we evaluated 81 American College of Medical Genetics (ACMG) medically actionable genes in 443 patients with various neurological disorders. The variants identified were classified and reported following the 2015 ACMG Standards and Guidelines for the interpretation of sequence variants and the ACMG recommendations for reporting secondary findings (v3.2). We detected a total of 17 variants in 17 patients across 9 different genes as secondary findings. Seven heterozygous variants were found in BRCA1, MSH2, and PALB2 which are part of the cancer phenotype category. Nine heterozygous variants were found in MYH7, TTN, LDLR, DSC2, and DSP which are part of the cardiovascular phenotype category. Finally, one heterozygous variant was found in TTR which is part of the miscellaneous phenotype category. Thirteen of above mentioned variants were classified as known pathogenic and four as expected pathogenic. The information collected in our study may lead to the prevention of severe morbidity and mortality and provides additional insight into the genetic background of the Serbian population.

Keywords: exome sequencing; gene testing; secondary findings; variants.

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References

REFERENCES

    1. Amendola, L. M., Dorschner, M. O., Robertson, P. D., Salama, J. S., Hart, R., Shirts, B. H., Murray, M. L., Tokita, M. J., Gallego, C. J., Kim, D. S., Bennett, J. T., Crosslin, D. R., Ranchalis, J., Jones, K. L., Rosenthal, E. A., Jarvik, E. R., Itsara, A., Turner, E. H., Herman, D. S., … Jarvik, G. P. (2015). Actionable exomic incidental findings in 6503 participants: Challenges of variant classification. Genome Research, 25(3), 305–315. https://doi.org/10.1101/gr.183483.114
    1. Antoniou, A. C., Casadei, S., Heikkinen, T., Barrowdale, D., Pylkäs, K., Roberts, J., Lee, A., Subramanian, D., De Leeneer, K., Fostira, F., Tomiak, E., Neuhausen, S. L., Teo, Z. L., Khan, S., Aittomäki, K., Moilanen, J. S., Turnbull, C., Seal, S., Mannermaa, A., … Tischkowitz, M. (2014). Breast‐cancer risk in families with mutations in PALB2. The New England Journal of Medicine, 371(6), 497–506. https://doi.org/10.1056/NEJMoa1400382
    1. Arslan Ateş, E., Türkyilmaz, A., Yıldırım, Ö., Alavanda, C., Polat, H., Demir, Ş., Çebi, A. H., Geçkinli, B. B., Güney, A. İ., Ata, P., & Arman, A. (2021). Secondary findings in 622 Turkish clinical exome sequencing data. Journal of Human Genetics, 66(11), 1113–1119. https://doi.org/10.1038/s10038‐021‐00936‐8
    1. Borry, P., Evers‐Kiebooms, G., Cornel, M. C., Clarke, A., & Dierickx, K., & Public and Professional Policy Committee (PPPC) of the European Society of Human Genetics (ESHG). (2009). Genetic testing in asymptomatic minors: Background considerations towards ESHG Recommendations. European Journal of Human Genetics: EJHG, 17(6), 711–719. https://doi.org/10.1038/ejhg.2009.25
    1. Brankovic, M., Ivanovic, V., Basta, I., Khang, R., Lee, E., Stevic, Z., Ralic, B., Tubic, R., Seo, G., Markovic, V., Bozovic, I., Svetel, M., Marjanovic, A., Veselinovic, N., Mesaros, S., Jankovic, M., Savic‐Pavicevic, D., Jovin, Z., Novakovic, I., … Peric, S. (2024). Whole exome sequencing in Serbian patients with hereditary spastic paraplegia. Neurogenetics, 25(3), 165–177. https://doi.org/10.1007/s10048‐024‐00755‐x Advance online publication