Screening of CNVs using NGS data improves mutation detection yield and decreases costs in genetic testing for hereditary cancer

J Med Genet. 2022 Jan;59(1):75-78. doi: 10.1136/jmedgenet-2020-107366. Epub 2020 Nov 20.


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.

Keywords: genetic testing; germ-line mutation; molecular diagnostic techniques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Costs and Cost Analysis
  • DNA Copy Number Variations*
  • Early Detection of Cancer*
  • Genetic Predisposition to Disease
  • Genetic Testing / economics
  • Genetic Testing / methods
  • High-Throughput Nucleotide Sequencing / economics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Mutation
  • Neoplasms / congenital
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Prospective Studies
  • Retrospective Studies
  • Sequence Analysis, DNA / economics
  • Sequence Analysis, DNA / methods
  • Software*