Fig. 2

Contribution of dnCNVs to statistical significance of DNM enrichment analyses. a A plot of q-values of DNM enrichment analyses for each gene before (x-axis) and after (y-axis) combining dnCNV data. The gray diagonal line indicates the line of y = x. The small inset is a magnified image. The dotted lines in the small inset: thresholds for exome-wide statistical significance (q-value = 0.05). b Visualization of the LOF dnCNVs affecting GLTSCR1 in a YCU case. From top to bottom, the plots show the exon–intron structures of the canonical transcripts, LOEUF, CNVs called by the exome hidden markov model (XHMM), and z scores of depth in the XHMM analysis. LOEUF of each gene is shown as a horizontal line corresponding to its genomic region. In the plot of z score for depth, the red line indicates the z score of the case with the LOF dnCNV, and the black lines indicate the z scores of 500 randomly selected control individuals. c IGV images of WGS data of a family with a UBR3 dnCNV (13302) and a family with a MARK2 dnCNV (12103). At the top, coverage and paired-end reads of all family members and exon–intron structures of genes are shown. At the bottom, magnified images of coverage and paired-end reads of the affected proband are shown. In the magnified images, discordant read pairs, whose read one and read two surround a dnCNV, are connected with a black line, and split reads, which span a breakpoint, are connected with a red line. p1, the affected proband; fa, the father; mo, the mother; s1, the healthy sibling