Table 2

BRCA2 alternate mRNA splicing events detected during phase II

BRCA 2 splice variant	HGVS nomenclature	Biotype	Functional annotation	CDS	Functional domains/biological activities predicted to be targeted*	LCL detection	MCF7	HCC1937	BT20	MCF10A	184A1	184B5	% positive cell lines in phase II	Previously reported in literature†
Δ2	r.-38_67del106	Cassette	Non-coding			9/11	+	+	+	+	+	–	82	No
Δ3	r.68_316del249	Cassette	No FS	p.Asp23_Leu105del	PALB2 bindingEMSY bindingTranscriptional activation	10/10	+	+	+	+	+	+	100	Yes
Δ3,4	r.68_c.425del359	Multicassette	PTC-NMD			11/11	–	+	+	–	+	–	82	No
Δ3–7	r.68_631del564	Multicassette	No FS	p.Asp23_Ile210del	PALB2 bindingEMSY bindingTranscriptional activation	9/11	+	+	+	+	+	+	88	No
Δ4	r.317_425del109	Cassette	PTC-NMD			8/11	–	+	+	–	–	–	59	No
Δ4–7	r.317_631del315	Multicassette	No FS	p.Gly106_Ile210del	CEP55-TSG111 binding CEP55-Alix binding	11/11	+	+	+	–	+	–	88	No
Δ5	r.426_475del50	Cassette	PTC-NMD			11/11	+	+	+	–	+	+	94	Yes
Δ5,6	r.426_516del91	Cassette	PTC-NMD			7/10	–	+	+	–	+	–	62	Yes
Δ5–7	r.426_631del206	Multicassette	PTC-NMD			10/11	–	+	+	+	+	+	88	No
Δ6	r.476_516del41	Cassette	PTC-NMD			4/10	+	+	+	–	+	–	50	Yes
▾5p‡	r.426-23_426-1ins 23	Cassette	PTC-NMD			5/10	–	–	+	+	+	–	50	No
Δ6q,7	r.478-631del154	Splice donor shift+cassette	PTC-NMD			7/10	+	+	+	+	+	+	81	No
Δ9–11§	r.682_6841del6160	Multicassette	PTC-NMD			2/11	–	–	+	–	+	–	29	No
Δ12¶**	r.6842_6937del96	Cassette	No FS	p.Glu2282_Gly2313del	None††	6/12	+	+	+	+	+	+	67	Yes
Δ12,13	r.6842_7007del166	Multicassette	PTC-NMD			6/11	+	+	+	–	+	+	65	No
Δ17**	r.7806_7976del171	Cassette	No FS	p.Ala2603_Arg2659del	DNA bindingDSS1 binding	9/10	–	–	+	–	+	–	69	No
Δ17,18	r.7806_8331del526	Multicassette	PTC-NMD			9/10	+	+	+	+	+	–	88	Yes
Δ18	r.7977_8331del355	Cassette	PTC-NMD			9/11	+	+	+	+	+	–	82	Yes
Δ19	r.8332_8487del156	Cassette	PTC-NMD			9/10	+	+	+	+	+	+	94	No
Δ20	r.8488_8632del145	Cassette	PTC-NMD			8/11	–	–	–	–	+	–	53	No
▾20A ‡‡	r.8633-1327_8633-1264ins64	Cassette	PTC-NMD			7/11	+	+	+	+	+	+	76	No
Δ22	r.8755_8953del199	Cassette	PTC-NMD			10/11	–	+	–	–	+	–	70	No
Δ22,23p	r.8755_9004del250	Cassette+splice acceptor shift	PTC-NMD			4/10	–	+	+	–	+	+	50	No
Δ23p	r.8954_9004del51	Splice acceptor shift	PTC-NMD			3/10	+	+	+	+	+	+	56	No
▾20A, Δ22	r.8633-1327_8633-1264ins64+8755_8953del199	Multicassette	PTC-NMD
▾20A, Δ22,23	r.8633-1327_8633-1264ins64+8755_9117del363	Multicassette	PTC-NMD
Δ11	r.1910_6841del4932	Cassette	No FS	p.Leu638_Val2280del	Rad51 bindingDNA recombination
Δ11,12	r.1910_6937del5028	Multicassette	No FS	p.Leu638_Gly2313del	Rad51 bindingDNA recombination
Δ11–13	r.1910_7008del5099	Multicassette	PTC-NMD

Alternate-splicing events, also indicated by their mRNA position, were detected in a subset of LCLs or breast cell lines as indicated. The references for those previously reported in the literature are Bieche et al,11 Claes et al,12 Farrugia et al,13 Hansen et al,14 Santarosa et al,15 Walker et al16 and Houdayer et al.17
Alternate splice variants in italics were identified after this work was completed and were not part of this study (see text).
*Predictions have been made based on the following BRCA2 protein domain definitions:49 binding to PALB2 and EMSY (residues 10–40), transcriptional activity (residues 24–105), binding to CEP55-TSG111 and CEP55-Alix (residues 200–600), Rad 51 binding (residues 638–2280), DNA and DSS1 binding domain (residues 2459–3190).
†References are listed in the table legend.
‡Predicted from a previous mutation analysis (see text). §Identified in ENCODE. ¶An additional LCL was tested for the Δ12 alternate-splicing event.
**GeneScan prediction/H-Inv 7.0 GenePrediction. ††Exon 12 has been reported to be functionally redundant.40
‡‡Ensemble transcript ENST00000528762.
CDS, coding sequence (predicted amino acids of the portion of the protein removed by the deletion); FS, frameshift; LCLs, lymphoblastoid cell lines; PTC-NMD, premature termination codon followed by a predicted nonsense-mediated mRNA decay.