Poster Session I Thursday, January 26 • 10:30 AM - 12:00 PM • Octavius Ballroom| Volume 216, ISSUE 1, SUPPLEMENT , S121, January 01, 2017

185: The impact of copy number analysis in expanded carrier screening


      To examine the impact of copy number variants (CNVs) on detection rates in expanded carrier screening (ECS) panels.

      Study Design

      ECS panels typically include analysis of copy number variation (CNV) for only a small subset of genes and exons, often to the detriment of detection rate. To assess the impact of panel-wide CNV analysis, a preliminary analysis was performed on 56,267 de-identified ECS tests performed by full-exon next-generation sequencing at Counsyl’s laboratory. A 93 gene subset (consisting of severe and profound diseases) of Counsyl’s ECS panel was analyzed to estimate the additional benefit of copy number analysis. The disease risk, i.e., the probability that a hypothetical child from randomly selected parents is affected by disease, was used as a metric for detection rate. No variant curation was performed on the detected CNVs and all detected deletions/duplications were assumed pathogenic. To calculate the disease risk, historical NGS data at Counsyl was used to estimate deleterious allele frequencies (AFs). The AFs were then used to calculate the disease risk with CNV estimates either excluded or included.


      Without CNV analysis, the disease risk of the 93 gene subpanel was 123 affected children per 100,000. The addition of CNV analysis increased the detection rate by 2.0%, to 125 affected children per 100,000. This change in disease risk is roughly equivalent to calling non-CNV variants via NGS in the 54 least prevalent genes, which contribute 2.0% of the observed disease risk.


      Panel-wide CNV analysis increases detection rate and provides more value than the addition of low-prevalence genes. CNV calling may be important to further reduce a patient’s residual risks for specific genes due to certain scenarios, e.g., family history of a genetic disease and partner testing of known carriers for recessive diseases. For example, in HBB, CFTR, and ATM, CNVs account for up to 9% of the total detection rate. Further work to assess the clinical impact of the discovered variants is ongoing.