ORIGINAL RESEARCH article
Front. Genet.
Sec. Human and Medical Genomics
Concordance between Genome-Wide cfDNA Screening and Diagnostic Test Results for Large Copy-Number Variants: A Multi-Site Study from the Global Expanded NIPT Consortium
Erica Soster 1
Kristin Dalton 2
Michael Bonifacio 3
Katie Battese Ellis 3,2
Tristan Hardy 4
Abdelkader Heddar 5
Monika Jurkowska 6
Pascale Kleinfinger 7
Marizela Kulisic 5
Kelly Loggenberg 8
Melody Menezes 4
Allesio Mori 9
Giovanni Savarese 9
Thomas Westover 10,11
Sucheta Bhatt 2
1. Labcorp Genetics and Women's Health, Westborough, MA, United States
2. Illumina Inc, San Diego, United States
3. Genea, Sydney, NSW, Australia
4. Monash IVF Group, Richmond, Australia
5. Laboratoire National de Sante, Dudelange, Luxembourg
6. Genomed SA, Warsaw, Poland
7. Laboratoire CERBA, Saint-Ouen-l'Aumône, France
8. Next Biosciences, Johannesburg, South Africa
9. Centro AMES, Casalnuovo di Napoli, Italy
10. Capital Health, Trenton, United States
11. Rowan University Cooper Medical School, Camden, United States
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Abstract
Fetal copy-number variants (CNVs) have been associated with a broad range of phenotypes and pregnancy outcomes. Noninvasive prenatal screening using genome-wide cell-free (cf) DNA analysis offers an opportunity to detect fetal CNVs early in pregnancy. This retrospective cohort study evaluated concordance between genome-wide cfDNA screening and diagnostic test results for 276 cases with a single isolated cfDNA-identified CNV >7 Mb. Cases for this study were submitted by members of the Global Expanded NIPT Consortium. Eight consortium sites in seven countries This is a provisional file, not the final typeset article contributed cases, with 83% of cases submitted from European sites. Seventy-three of 276 cases (26.5%) had no known high-risk indication for cfDNA screening. Mean and median gestational age at the time of cfDNA blood draw was 13 weeks. A deletion was identified for 124 (44.9%) cases and a duplication for 152 (55.1%) cases. Mean CNV size was 33.4 Mb (median 23.1 Mb, range 7–187 Mb). Diagnostic test results were available for 209/276 cases (75.7%). Concordance between cfDNA screening and diagnostic test results was observed for 49/209 cases (23.4%). Mean and median fetal fraction among concordant cases was 8.8% and 8%, respectively. Among 157 discordant cases, a plausible maternal biological explanation was identified for 21 cases (13.4%). Pregnancy outcome information was limited, but available for 116 (42.0%) cases. Parental testing results were available for 38 (13.8%) cases. For six of 15 concordant cases with parental results, fetal CNVs were secondary to a parental translocation or rearrangement. This study contributes to the growing evidence supporting the use of genome-wide cfDNA screening for detection of large fetal CNVs that could affect the current pregnancy and future reproductive risks as well as identify previously unknown maternal conditions.
Summary
Keywords
cell-free DNA, Copy-number variants, deletions, Duplications, genome-wide, Noninvasive prenatal testing
Received
11 November 2025
Accepted
19 February 2026
Copyright
© 2026 Soster, Dalton, Bonifacio, Ellis, Hardy, Heddar, Jurkowska, Kleinfinger, Kulisic, Loggenberg, Menezes, Mori, Savarese, Westover and Bhatt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Erica Soster
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