PT - JOURNAL ARTICLE AU - José Marcos Moreno-Cabrera AU - Jesús del Valle AU - Lidia Feliubadaló AU - Marta Pineda AU - Sara González AU - Olga Campos AU - Raquel Cuesta AU - Joan Brunet AU - Eduard Serra AU - Gabriel Capellà AU - Bernat Gel AU - Conxi Lázaro TI - Screening of CNVs using NGS data improves mutation detection yield and decreases costs in genetic testing for hereditary cancer AID - 10.1136/jmedgenet-2020-107366 DP - 2020 Nov 20 TA - Journal of Medical Genetics PG - jmedgenet-2020-107366 4099 - http://jmg.bmj.com/content/early/2020/11/20/jmedgenet-2020-107366.short 4100 - http://jmg.bmj.com/content/early/2020/11/20/jmedgenet-2020-107366.full AB - Introduction Germline CNVs are important contributors to hereditary cancer. In genetic diagnostics, multiplex ligation-dependent probe amplification (MLPA) is commonly used to identify them. However, MLPA is time-consuming and expensive if applied to many genes, hence many routine laboratories test only a subset of genes of interest.Methods and results We evaluated a next-generation sequencing (NGS)-based CNV detection tool (DECoN) as first-tier screening to decrease costs and turnaround time and expand CNV analysis to all genes of clinical interest in our diagnostics routine. We used DECoN in a retrospective cohort of 1860 patients where a limited number of genes were previously analysed by MLPA, and in a prospective cohort of 2041 patients, without MLPA analysis. In the retrospective cohort, 6 new CNVs were identified and confirmed by MLPA. In the prospective cohort, 19 CNVs were identified and confirmed by MLPA, 8 of these would have been lost in our previous MLPA-restricted detection strategy. Also, the number of genes tested by MLPA across all samples decreased by 93.0% in the prospective cohort.Conclusion Including an in silico germline NGS CNV detection tool improved our genetic diagnostics strategy in hereditary cancer, both increasing the number of CNVs detected and reducing turnaround time and costs.