Since 2014, GeneDx has been detecting copy number variants (CNVs) directly from exome sequencing data using an in-house developed algorithm.1
This method can reliably detect most deletions and duplications involving three or more coding exons; smaller deletions or duplications may not be reliably identified. All reported CNVs are confirmed by an orthogonal method such as array CGH, MLPA, or PCR and parental confirmations for reportable CNVs are reported without additional charges. CNV analysis may not be possible in a subset of specimens. All Xome-based reports will include whether CNV detection was possible. At this time, exome based technology is not a replacement for the sensitivity of exon level aCGH.
Our CNV analysis via XomeDx® can identify:
- Large multi-gene chromosomal aberrations
- Small, partial gene, and intragenic CNVs; deletions and duplications of three exons or larger are reliably identified
- CNVs of one to two exons in size may be identified and comprise >50% of our previously reported exon-level variants
- Chromosomal aneuploidy
- Uniparental disomy (UPD), including isodisomy and heterodisomy
- Inheritance of CNVs when a trio is submitted
CNV analysis is limited or may not be possible in regions with reduced coverage, extreme GC- or AT-content, or significant homology to pseudogenes or segmental duplications. Our method may not always detect balanced aberrations, mosaicism, deletions/duplications involving only part of an exon, or CNVs in non-coding regions of the genome.
1. Retterer K, Scuffins J, Schmidt D, et al. Assessing copy number from exome sequencing and exome array CGH based on CNV spectrum in a large clinical cohort. Genetics in Medicine: Official Journal of the American College of Medical Genetics. 2015;17(8):623-629. doi:10.1038/gim.2014.160.