Actionable genomic variants in 6045 participants from the Qatar Genome Program
Amal Elfatih, Borbála Mifsud, Najeeb Syed, Ramin Badii, Hamdi Mbarek, Fatemeh Abbaszadeh, Xavier Estivill, Qatar Genome Project Management, Said I. Ismail, Wadha Al‐Muftah, Radja Badji, Hamdi Mbarek, Dima Darwish, Tasnim Fadl, Heba Yasin, Maryem Ennaifar, Rania G. Abdel‐latif, Fatima Alkuwari, Muhammad Arshad Alvi, Yasser Al‐Sarraj, Chadi Saad, Asmaa Althani, Biobank and Sample Preparation, Eleni Fethnou, Fatima Qafoud, Eiman Alkhayat, Nahla Afifi, Sequencing and Genotyping group, Sara Tomei, Wei Liu, Stephan Lorenz, Applied Bioinformatics Core, Najeeb Syed, Hakeem Almabrazi, Fazulur Rehaman Vempalli, Ramzi Temanni, Data Management and Computing Infrastructure group, Tariq Abu Saqri, Mohammedhusen Khatib, Mehshad Hamza, Tariq Abu Zaid, Ahmed El Khouly, Tushar Pathare, Shafeeq Poolat, Rashid Al‐Ali, Omar Albagha, Souhaila Al Khodor, Mashael Al‐Shafai, Ramin Badii, Lotfi Chouchane, Xavier Estivill, Khalid A. Fakhro, Hamdi Mbarek, Younes Mokrab, Puthen V. Jithesh, Karsten Suhre, Zohreh Tatari-Calderone
Abstract
In a clinical setting, DNA sequencing can uncover findings unrelated to the purpose of genetic evaluation. The American College of Medical Genetics and Genomics (ACMG) recommends the evaluation and reporting of 59 genes from clinic genomic sequencing. While the prevalence of secondary findings is available from large population studies, these data lack Arab and other Middle Eastern populations. The Qatar Genome Program (QGP) generates whole-genome sequencing (WGS) data and combines it with phenotypic information to create a comprehensive database for studying the Qatari and wider Arab and Middle Eastern populations at the molecular level. This study identified and analyzed medically actionable variants in the 59 ACMG genes using WGS data from 6045 QGP participants. Our results identified a total of 60 pathogenic and likely pathogenic variants in 25 ACMG genes in 141 unique individuals. Overall, 2.3% of the QGP sequenced participants carried a pathogenic or likely pathogenic variant in one of the 59 ACMG genes. We evaluated the QGP phenotype-genotype association of additional nonpathogenic ACMG variants. These variants were found in patients from the Hamad Medical Corporation or reported incidental findings data in Qatar. We found a significant phenotype association for two variants, c.313+3A>C in LDLR, and c.58C>T (p.Gln20*) in the TPM1.