Validation of Copy Number Variants Detection from Pregnant Plasma Using Low-Pass Whole-Genome Sequencing in Noninvasive Prenatal Testing-Like Settings

Hyblova, M.1,2, Harsanyova, M.3, Nikulenkov-Grochova4, D., Kadlecova, J.4, Kucharik, M.3, Budis, J.3, Minarik, G.1,2

1Trisomy Test s.r.o., Ilkovičova 8, 841 04 Bratislava, Slovakia
2Medirex a.s., Galvaniho 17/C, 821 06 Bratislava, Slovakia
3Geneton s.r.o, Galvaniho 7, 821 06 Bratislava, Slovakia
4Cytogenetic laboratory Brno s.r.o., Veveri 39, 602 00 Brno, Czech Republic


Detection of copy number variants as an integral part of noninvasive prenatal testing is increasingly used in clinical practice worldwide. We performed validation on plasma samples from 34 pregnant women with known aberrations using cell-free DNA sequencing to evaluate the sensitivity for copy number variants (CNV) detection using an in-house CNV fraction-based detection algorithm. The sensitivity for CNVs smaller than 3 megabases (Mb), larger than 3Mb, and overall was 78.57%, 100%, and 90.6%, respectively. Regarding the fetal fraction, detection sensitivity in the group with a fetal fraction of less than 10% was 57.14%, whereas there was 100% sensitivity in the group with fetal fraction exceeding 10%. The assay is also capable of indicating whether the origin of an aberration is exclusively fetal or fetomaternal/maternal. This validation demonstrated that a CNV fraction-based algorithm was applicable and feasible in clinical settings as a supplement to testing for common trisomies 21, 18, and 13.