Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation

Table 1 Most common pathogenic BRCA1 and BRCA2 variants in ExAC

Gene	Variant	Effect	Allele count	MAF	Type
BRCA1	NM_007294.3:c.68_69delAG	p.Glu23Valfs*17	29	0.024%	Founder [24]
BRCA1	NM_007294.3:c.5266dupC	p.Gln1756Profs*74	19	0.016%	Founder [24]
BRCA1	NM_007294.3:c.181 T > G	p.Cys61Gly	8	0.0067%	Founder [36]
BRCA1	NM_007294.3:c.4035delA	p.Glu1346Lysfs*20	5	0.0041%	Founder [37]
BRCA1	NM_007294.3:c.1687C > T	p.Gln563*	5	0.0041%	Founder [38]
BRCA2	NM_000059.3:c.5946delT	p.Ser1982Argfs*22	32	0.027%	Founder [24]
BRCA2	NM_000059.3:c.3847_3848delGT	p.Val1283Lysfs*2	11	0.011%	Recurrent [39]
BRCA2	NM_000059.3:c.658_659delGT	p.Val220Ilefs*4	6	0.0061%	Recurrent [40, 41]
BRCA2	NM_000059.3:c.7480C > T	p.Arg2494*	6	0.0050%	Founder [42]
BRCA2	NM_000059.3:c.3545_3546delTT	p.Phe1182*	4	0.0033%	Recurrent [43, 44]
BRCA2	NM_000059.3:c.3599_3600delGT	p.Cys1200*	4	0.0033%	Recurrent [45]
BRCA2	NM_000059.3:c.5576_5579delTTAA	p.Ile1859Lysfs*3	4	0.0033%	Recurrent [46, 47]
BRCA2	NM_000059.3:c.7069_7070delCT	p.Leu2357Valfs*2	4	0.0033%	Recurrent [48]
BRCA2	NM_000059.3:c.9118-2A > G	Splice acceptor	4	0.0033%	Recurrent [39, 49]

Fourteen pathogenic variants in BRCA1 and BRCA2 were observed in more than three individuals in the ExAC cohort. All of these variants have been previously reported as founder or common recurrent variants. Some of these recurrent variants are suggested to be founder mutations, but have not been confirmed as such. MAF minor allele frequency

ISSN: 1756-994X