Table 2.
Spectrum and functional classification of germline BRCA1/2 variants according to gene and pathogenicity
| Variant category | BRCA1 Pathogenic (n = 47) |
BRCA2 Pathogenic (n = 60) |
BRCA1 VUS (n = 32) |
BRCA2 VUS (n = 64) |
p value† |
|---|---|---|---|---|---|
| Functional class | < 0.001 | ||||
| Truncating (LoF) | 33 (70.2%) | 51(85%) | 0 (0%) | 4 (6.3%) | |
| Non-truncating coding | 10 (21%) | 6 (10%) | 25(78.1%) | 54 (84.4%) | |
| Non-coding / other | 1 (2.1%) | 0 (0%) | 7 (21.9%) | 6 (9.4%) | |
|
Biological Effect of Mutation |
< 0.001 | ||||
| Frameshift | 14 (29.7%) | 35 (58.3%) | 0 (0%) | 3 (4.7%) | |
| Nonsense | 8 (17%) | 12 (20%) | 0 (0%) | 1 (1.6%) | |
| Missense | 10 (21.2%) | 5(8.3%) | 22 (68.8%) | 47 (73.4%) | |
| Splice-site | 3 (6.3%) | 3(5%) | 0(0%) | 0 (0%) | |
| Indel | 7(14.8%) | 2 (3.3%) | 2 (6.3%) | 4 (6.3%) | |
| Other / intronic | 1 (2.1%) | 0 (0%) | 8(25%) | 9 (14.1%) |
† p values were calculated using the chi-square test of independence for the overall distribution across the four groups. Data are presented as number (%). Truncating variants include frameshift, nonsense, canonical splice-site alterations, and large genomic rearrangements. Percentages are calculated within each column. Bold values indicate statistically significant results (p < 0.05)