Table 2.

Variants prioritized by IT analysis

Patient ID	Gene	mRNA	rsID (dbSNP 142)	Information Change			Consequencef or Binding Factor Affected
				R i,initial	R i,final	ΔR i or R i e
			Allele Frequency (%)d	(bits)	(bits)	(bits)
Abolished Natural SS
7-4 F	ATM	c.3747-1G > Aa	Novel	11.0	0.1	−10.9	Exon skipping and use of alternative splice forms
4-1 F	ATM	c.6347 + 1G > Tb	Novel	10.4	−8.3	−18.6	Exon skipping
Leaky Natural SS
4-2B	CHEK2	c.320-5 T > Aa	rs121908700	6.8	4.1	−2.7	Leaky splicing with intron inclusion
			0.08
Activated Cryptic SS
7-3E	BRCA1	c.548-293G > A	rs117281398	−12.1	2.6	14.7	Cryptic site not expected to be used. Total information for natural exon is stronger than cryptic exon.
			0.74
7-4A	BRCA2	c.7618-269_7618-260del10	Novel	3.9	9.4	5.5	Cryptic site not expected to be used. Total information for natural exon is stronger than cryptic exon.
Pseudoexon formation due to activated acceptor SS
7-3 F	BRCA2	c.8332-805G > A	Novel	−9.3	5.4	5.6e	6065/211/592f
7-3D	CDH1	c.164-2023A > G	rs184740925	−6.6	4.3	6.5e	61,236/224/1798f
			0.3
5-3H	CDH1	c.2296-174 T > A	rs565488866	7.3	8.5	5.0e	1175/50/124f
			0.02
Pseudoexon formation due to activated donor SS
3-6A	BRCA1	c.212 + 253G > A	rs189352191	4.1	6.7	5.2e	186/63/1250f
			0.08
5-2G	BRCA2	c.7007 + 2691G > A	rs367890577	4.7	7.2	7.7e	2589/103/5272f
			0.02
Affected TFBSs
7-4B	BRCA1	c.-8895G > A	Novel	10.9	−0.2	−11.1	GATA-3 (GATA3)
5-3E	CDH1	c.-54G > C	rs5030874	1.7	12.0	10.4	E2F-4 (E2F4)
7-4E			0.16
5-2B	PALB2	c.-291C > G	rs552824227	12.1	−1.3	−13.4	GABPα (GABPA)
			0.1
7-2 F	TP53	c.-28-3132 T > C	rs17882863	−6.3	10.9	17.2	RUNX3 (RUNX3)
			0.3
4-1A	TP53	c.-28-1102 T > C	rs113451673	5.1	12.3	7.2	E2F-4 (E2F4)
			0.4	8.0	12.9	4.8	Sp1 (SP1)
Affected RBBSs
7-4G	ATM	c.-244 T > A	rs539948218	9.8	−19.9	−29.7	RBFOX
		c.-744 T > A	0.04
		c.-1929 T > A
		c.-3515 T > A
5-3C	CDH1	c.*424 T > A	Novel	−20.3	9.6	29.9	SF3B4
				8.2	1.8	−6.4	CELF4
7-2E	CHEK2	c.-588G > A	rs141568342	10.9	3.7	−7.2	BX511012.1
4-3C.5-4G	CHEK2	c.-345C > Tc	rs137853007	3.3	11.4	8.2	SF3B4
3-1A	TP53	c.-107 T > C	rs113530090	10.5	4.5	−6.0	ELAVL1
4-1H		c.-188 T > C	0.72
4-2H	TP53	c.*1175A > C	rs78378222	10.7	4.1	−6.6	KHDRBS1
7-2 F		c.*1376A > C	0.26
		c.*1464A > C

^aConfirmed by Sanger sequencing

^bAmbiguous Sanger sequencing results

^cPrioritized under missense change and was therefore verified with Sanger sequencing. Variant was confirmed

^dIf available

^e R _i of site of opposite polarity in the pseudoexon

^fConsequences for pseudoexon formation describe how the intron is divided: “new intron A length/pseudoexon length/new exon B length

None of the variants have been previously reported by other groups with the exception of CHEK2 c.320-5T>A [148]