Table 1.
Pathogenic CNVs analyzed in a pilot study correctly identified by ExomeDepth and ploidy analysis.
Table 2.
Performance of WES-based CNV detection for “known” CNVs detected by clinical microarray.
Fig 1.
Mean number of deletions and duplications per person meeting filtering criteria.
Top panels compare deletions and duplications < 100 kb. Bottom panels compare CNV > 100 kb. Left panels show numbers of deletions and right panels show duplications. Overall, there are more deletions with high Bayes factor scores per person than duplications with high Bayes factor scores. However, more duplications were detected that met multiple filtering criteria. Additionally, predicted CNV with a size > 100 kb were more likely to meet ISCA and number of exon criteria.
Table 3.
CNVs of potential diagnostic significance detected in NCGENES patients.
Table 4.
CNVs with unknown clinical significance due to uncertain pathogenicity or unclear phenotypic overlap.
Fig 2.
Orthogonal CNV detection methods confirm a DYNC2H1 duplication in an anomalous fetus.
A. An intron-exon map of the DYNC2H1 gene is depicted with respect to hg19 genomic coordinates (note nearby genes are not indicated for simplicity). Also shown are the locations of the fluorescence in situ hybridization (FISH) probes (RP11-450C20, RP11-2I22, and RP11-213G10), the pathogenic SNV (red) identified by WES, the Real-Time PCR probe (green), and the approximate coordinates of the paternal duplication identified by ExomeDepth (ED) in aqua and by the GSA array in orange. B. An interphase FISH image shows an enhanced/duplicated red signal flanked by a green signal on either side, indicative of a tandem duplication. C., D. Metaphase FISH analysis shows an enhanced red signal, representing the duplicated region, isolated to chromosome 11. Panel D shows an isolated view of both chromosome 11 homologs from a second metaphase cell. DAPI stain was converted to black and white for better visualization of red and green signals.