Table 2b.

MAF of BRCA2 sequence VUS^a, identified in women with CBC or UBC.

Typeb	MAF	CBC	UBC	Relative Risk (95%CI) c,d
Missense
102 unique variants	<0.1%	46	72	1.4 (0.9–2.0)
10 unique variants	0.1–0.5%	24	57	0.9 (0.5–1.5)
4 unique variants	0.5–2.5%	22	64	0.7 (0.4–1.2)
T1915M	2.6%	26	74	0.8 (0.5–1.2)
N289H	3.5%	44	92	1.1 (0.7–1.6)
N991D	3.5%	43	92	1.0 (0.7–1.5)
N372H	28%	310	627	1.2 (1.0–1.4)
Synonymous
40 unique variants	<0.1%	18	34	1.2 (0.7–2.2)
6 unique variants	0.1–0.5%	19	37	1.1 (0.6–2.0)
no variant	0.5–2.5%	-	-	-
H743H	3.4%	42	90	1.0 (0.7–1.5)
S455S	3.5%	44	89	1.1 (0.7–1.6)
V1269V	16%	177	419	0.9 (0.7–1.1)
S2414S	19%	207	477	1.0 (0.8–1.2)
K1132K	23%	267	581	1.1 (0.9–1.3)
IVS
41 unique variants	<0.1%	20	33	1.4 (0.8–2.5)
8 unique variants	0.1–0.5%	20	48	0.9 (0.5–1.6)
1 unique variants	0.5–2.5%	8	23	0.7 (0.3–1.6)
IVS16−14T>C	28%	325	689	1.1 (0.9–1.3)

^aIndividuals with rare variants are aggregated within MAF categories. Common variants (MAF>2.5%) are listed separately. Frequencies correspond to combined frequencies of heterozygotes or homozygote variants.

^bIn addition to the variants listed, 3 women with CBC and 3 women with UBC had rare variants that were either in-frame deletions, frameshifts, nonsense mutations or variants in the untranslated regions (UTR). In addition there is a 5′ UTR polymorphism (203G>A) that was observed in 269 CBC and 528 UBC (OR=1.0). BRCA2 (GenBank NM_000059.1) mutation nomenclature according to BIC. IVS=intervening sequence (noncoding). Mutation nomenclature according to HGVS is found in Supp. Table S1.

^c95% confidence interval.

^dThe reference group for each RR consists of women carrying all other types of VUSs and excludes carriers of known deleterious BRCA mutations.