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Table 1 Variants with altered transcripts

From: Diagnostic mRNA splicing assay for variants in BRCA1 and BRCA2 identified two novel pathogenic splicing aberrations

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  
  1. Splice class as defined by Houdayer 2012; 3S: Severe impact on splicing/the mutant allele does not produce the wildtype transcript, complete effect, 2S: impact on alternative splicing/leaky splice site mutation, partial effect, NA not analyzed