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Table 2 Variants prioritized by IT analysis

From: A unified analytic framework for prioritization of non-coding variants of uncertain significance in heritable breast and ovarian cancer

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
  1. aConfirmed by Sanger sequencing
  2. bAmbiguous Sanger sequencing results
  3. cPrioritized under missense change and was therefore verified with Sanger sequencing. Variant was confirmed
  4. dIf available
  5. e R i of site of opposite polarity in the pseudoexon
  6. fConsequences for pseudoexon formation describe how the intron is divided: “new intron A length/pseudoexon length/new exon B length
  7. None of the variants have been previously reported by other groups with the exception of CHEK2 c.320-5T>A [148]
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BMC Medical Genomics

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