Mutation/unclassified variant status | None | First degree | Second degree | ||||
---|---|---|---|---|---|---|---|
 | n a | n a | OR (95% CI)b | P valuec | n a | OR (95% CI)b | P valuec |
BRCA1 d | |||||||
Normal/polymorphism (reference) | 600 | 166 | 1 | Â | 282 | 1 | Â |
Definitely disease-causing variant | 13 | 35 | 11.3 (5.73 to 22.5) | <0.001 | 11 | 1.89 (0.83 to 4.31) | 0.13 |
Unclassified variant | 156 | 67 | 1.54 (1.10 to 2.15) | 0.012 | 75 | 1.02 (0.74 to 1.39) | 0.90 |
Unclassified variant classification using | |||||||
Allele frequency | |||||||
   High risk (LFUV) | 39 | 21 | 2.00 (1.14 to 3.51) | 0.016 | 22 | 1.20 (0.70 to 2.06) | 0.52 |
   Low risk (HFUV) | 115 | 42 | 1.30 (0.87 to 1.93) | 0.20 | 52 | 0.96 (0.67 to 1.37) | 0.82 |
Polyphene | |||||||
   Probably damaging missense | 7 | 7 | 3.39 (1.16 to 9.94) | 0.026 | 6 | 1.80 (0.60 to 5.40) | 0.30 |
   Possibly damaging missense | 9 | 1 | 0.44 (0.06 to 3.54) | 0.44 | 5 | 1.19 (0.40 to 3.60) | 0.75 |
   Benign missense | 133 | 57 | 1.53 (1.07 to 2.18) | 0.021 | 61 | 0.97 (0.70 to 1.36) | 0.87 |
Sequence conservatione | |||||||
   High or moderatef | 50 | 23 | 1.68 (0.99 to 2.85) | 0.053 | 32 | 1.35 (0.85 to 2.16) | 0.20 |
   High | 6 | 3 | 1.88 (0.46 to 7.63) | 0.38 | 8 | 2.85 (0.98 to 8.30) | 0.055 |
   Moderate | 44 | 20 | 1.66 (0.95 to 2.91) | 0.076 | 23 | 1.10 (0.65 to 1.86) | 0.72 |
   Low | 99 | 40 | 1.43 (0.95 to 2.16) | 0.085 | 41 | 0.88 (0.60 to 1.31) | 0.53 |
Grantham matrix scoree | |||||||
   High (>60) | 15 | 10 | 2.38 (1.04 to 5.45) | 0.039 | 10 | 1.42 (0.63 to 3.20) | 0.40 |
   Low (≤ 60) | 134 | 55 | 1.46 (1.02 to 2.10) | 0.039 | 63 | 1.00 (0.72 to 1.39) | 0.98 |
Grantham matrix score/sequence conservatione | |||||||
   Deleterious | 4 | 2 | 1.74 (0.32 to 9.64) | 0.52 | 3 | 1.63 (0.36 to 7.33) | 0.53 |
   Intermediate (unclassified) | 46 | 22 | 1.75 (1.02 to 3.01) | 0.043 | 25 | 1.15 (0.69 to 1.91) | 0.60 |
   Neutral | 99 | 40 | 1.44 (0.95 to 2.16) | 0.083 | 44 | 0.95 (0.65 to 1.39) | 0.78 |
BRCA2 g | |||||||
Normal/polymorphism (reference) | 279 | 87 | 1 | Â | 137 | 1 | Â |
Definitely disease-causing variant | 11 | 13 | 3.69 (1.57 to 8.68) | 0.003 | 10 | 1.83 (0.76 to 4.42) | 0.18 |
Unclassified variant | 462 | 162 | 1.07 (0.79 to 1.46) | 0.66 | 213 | 0.93 (0.72 to 1.21) | 0.59 |
Unclassified variant classification using | |||||||
Allele frequency | |||||||
   High risk (LFUV) | 71 | 18 | 0.81 (0.45 to 1.45) | 0.48 | 40 | 1.15 (0.74 to 1.78) | 0.54 |
   Low risk (HFUV) | 385 | 138 | 1.09 (0.79 to 1.50) | 0.59 | 168 | 0.88 (0.67 to 1.16) | 0.36 |
Polyphene | |||||||
   Probably damaging missense | 32 | 7 | 0.73 (0.31 to 1.74) | 0.48 | 17 | 1.09 (0.58 to 2.03) | 0.79 |
   Possibly damaging missense | 108 | 28 | 0.79 (0.48 to 1.29) | 0.34 | 42 | 0.78 (0.52 to 1.18) | 0.24 |
   Benign missense | 310 | 118 | 1.15 (0.83 to 1.60) | 0.41 | 146 | 0.95 (0.72 to 1.26) | 0.73 |
Sequence conservatione | |||||||
   High or moderate | 157 | 42 | 0.80 (0.52 to 1.23) | 0.31 | 61 | 0.78 (0.55 to 1.12) | 0.18 |
   High | 96 | 30 | 0.92 (0.56 to 1.51) | 0.75 | 41 | 0.86 (0.57 to 1.31) | 0.48 |
   Moderate | 61 | 12 | 0.61 (0.31 to 1.21) | 0.15 | 20 | 0.66 (0.38 to 1.14) | 0.13 |
   Low | 292 | 113 | 1.18 (0.84 to 1.65) | 0.33 | 142 | 0.98 (0.74 to 1.31) | 0.91 |
Grantham matrix scoree | |||||||
   High (>60) | 450 | 155 | 1.05 (0.77 to 1.43) | 0.76 | 205 | 0.92 (0.71 to 1.20) | 0.53 |
   Low (≤ 60) | 9 | 3 | 0.98 (0.25 to 3.85) | 0.98 | 5 | 1.11 (0.37 to 3.39) | 0.85 |
Grantham matrix score/sequence conservatione | |||||||
   Deleterious | 124 | 34 | 0.83 (0.52 to 1.31) | 0.42 | 51 | 0.83 (0.56 to 1.22) | 0.34 |
   Intermediate (unclassified) | 66 | 14 | 0.67 (0.35 to 1.27) | 0.22 | 28 | 0.87 (0.53 to 1.41) | 0.56 |
   Neutral | 259 | 107 | 1.24 (0.89 to 1.75) | 0.21 | 124 | 0.97 (0.72 to 1.30) | 0.82 |