Table 1 Variants with altered transcripts
Gene | HGVS | Prediction/indication | Result mRNA | Splice class | Consequence | Previous publication and conclusion |
|---|---|---|---|---|---|---|
BRCA1 | c.4484G > A | Reduced donor site | r.4358_4484del, p.(Ala1453Glyfs*10) | NA | Exon 13 skipped out of frame | Houdayer 2012: severe impact on splicing (RT-PCR) (“Exon 14 skipped”) |
BRCA1 | c.4484 + 3A > C | Reduced donor site | r.4358_4484del, p.(Ala1453Glyfs*10) | 3S | Exon 13 skipped, out of frame, complete | |
BRCA1 | c.4675G > A | Loss of donor site | r.4665_4675del, p.Gln1556Glyfs*14 | 3S | Loss of last 11 bp in exon 14, out of frame, complete | Wappenschmidt 2012: severe impact on splicing (RT-PCR) (“D11nt 3′ of exon 15”) |
BRCA1 | c.5332 + 4A > G | Reduces donor site | r.5278_5332del, p.(Phe1761Asnfs*14) | NA | Exon 20 skipped, out of frame | |
BRCA1 | c.5407–10G > A | Loss of acceptor + activation of cryptic | r.5406_5407ins5407-8_5407–1, p.(Val1804Serfs*33) | 3S | Retention of 8 bp of intron 21, out of frame, complete | |
BRCA2 | c.631 + 4A > G | Reduced donor site | r. 517_631del, p.(Gly173Serfs*19) | 3S | Exon 7 skipped, out of frame, complete | Steffensen 2010: disease causing (minigene + RT-PCR) |
BRCA2 | c.7992 T > A | Slightly reduced acceptor site | r.7977_8331del p.(Tyr2660Phefs*43) | 2S | Exon 18 skipped, out of frame, partial | Fackenthal 2016: minor alternate transcript (∆18) (RT-PCR) |
BRCA2 | c.8331 + 2 T > C | Reduced donor site | r.7977_8331del p.(Tyr2660Phefs*43) | NA | Exon 18 skipped, out of frame, complete | Fraile-Bethencourt 2017: pathogenic (minigene) |
BRCA2 | c.8754 + 5G > C | Reduced donor site + activation of cryptic | r.8754_8755ins8754 + 1_8754 + 46, p.Gly2919Valfs*4 | NA | Retention of 46 bp of intron 21, out of frame |