Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program

Katherine E. Bonini, Amanda Thomas-Wilson, Priya N. Marathe, Monisha Sebastin, Jacqueline A. Odgis, Miranda Di Biase, Nicole R. Kelly, Michelle A. Ramos, Beverly J. Insel, Laura Scarimbolo, Atteeq U. Rehman, Saurav Guha, Volkan Okur, Avinash Abhyankar, Shruti Phadke, Caroline Nava, Katie M. Gallagher, Lama Elkhoury, Lisa Edelmann, Randi E. ZinbergNoura S. Abul-Husn, George A. Diaz, John M. Greally, Sabrina A. Suckiel, Carol R. Horowitz, Eimear E. Kenny, Melissa Wasserstein, Bruce D. Gelb, Vaidehi Jobanputra

Research output: Contribution to journalArticlepeer-review


Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0–21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.

Original languageEnglish
Pages (from-to)210-225
Number of pages16
JournalClinical Genetics
Issue number2
StatePublished - Aug 2023


  • CNV
  • clinical genomics
  • copy number variation
  • diagnostic testing
  • diverse populations
  • genome sequencing
  • pediatric genomics


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