Table 1.
Rates of detection of BRCA1/2 and non BRCA breast/ovarian pathogenic variants by Manchester score.
| Manchester Score | ≤8 | 9–10 | 11–12 | 13–14 | 15–19 | 20–24 | 25–29 | 30–39 | ≥40 | Total PVs Cases | PROCAS Controls PVs | OR | 95% CI | p-Value |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Full extended panel cohort | ||||||||||||||
| BRCA1 | 1 | 0 | 0 | 0 | 2 | 3 | 3 | 9 | 8 | 26 | 2 | NA | NA | NA |
| BRCA2 | 5 | 1 | 1 | 4 | 11 | 4 | 9 | 7 | 1 | 43 | 6 | NA | NA | NA |
| ATM | 7 | 2 | 1 | 3 | 7 | 5 | 3 | 3 | 0 | 31 | 5 | 6.52 | 2.56–15.55 | <0.0001 |
| CHEK2 | 12 | 0 | 1 | 2 | 4 | 2 | 0 | 3 | 1 | 25 | 3 | 8.74 | 2.88–27.60 | <0.0001 |
| TP53 * | 3 | 0 | 0 | 0 | 4 | 1 | 1 | 0 | 1 | 10 | 0 | 36.02 | 6.33–392.1 | <0.0001 |
| PALB2 | 2 | 3 | 3 | 1 | 6 | 6 | 3 | 0 | 0 | 24 | 3 | 8.38 | 2.74–26.53 | <0.0001 |
| NBN | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 2 | 1.55 | 0.32–8.75 | 0.6825 |
| CDH1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | n/a | ||
| RAD51C | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | n/a | ||
| RAD51D | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | n/a | ||
| BRIP1 | 1 | 0 | 0 | 2 | 1 | 3 | 0 | 0 | 0 | 7 | 2 | 3.63 | 0.82–17.31 | 0.1037 |
| BARD1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1.03 | 0.05–19.62 | >0.9999 |
| PTEN | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | n/a | ||
| Total PVs | 34 | 7 | 6 | 13 | 36 | 24 | 21 | 22 | 11 | 174 | 24 | |||
| Total tested | 525 | 78 | 91 | 106 | 255 | 149 | 95 | 72 | 27 | 1398 | 1443 | |||
| % PVs | 6.5% | 9.0% | 6.6% | 12.3% | 14.1% | 16.1% | 22.1% | 30.6% | 40.7% | 12.4% | 1.7% | |||
| Total non-BRCA PVs | 28 | 6 | 5 | 9 | 23 | 17 | 9 | 6 | 2 | 105 | ||||
| % non-BRCA PVs | 5.3% | 7.7% | 5.5% | 8.5% | 9.0% | 11.4% | 9.5% | 8.3% | 7.4% | 7.5% | ||||
| % adjusted for all BRCA1/2 tested | 5.3% | 7.4% | 5.3% | 8.0% | 8.1% | 8.8% | 6.4% | 3.6% | 1.5% | 6.4% | ||||
| No pre-screen | ||||||||||||||
| BRCA1 | 1 | 0 | 0 | 0 | 2 | 3 | 3 | 9 | 8 | 26 | 2 | 21.00 | 5.41–90.02 | <0.0001 |
| BRCA2 | 5 | 1 | 1 | 4 | 11 | 4 | 9 | 7 | 1 | 43 | 6 | 11.77 | 5.05–25.65 | <0.0001 |
| ATM | 6 | 2 | 0 | 3 | 3 | 3 | 1 | 1 | 0 | 19 | 5 | 6.08 | 2.43–14.96 | <0.0001 |
| CHEK2 | 12 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 13 | 3 | 6.89 | 2.04–22.80 | 0.001 |
| TP53 * | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 10.91 | 1.27–158.2 | 0.0647 |
| PALB2 | 2 | 3 | 0 | 0 | 3 | 3 | 2 | 0 | 0 | 13 | 3 | 6.89 | 2.04–22.80 | 0.001 |
| NBN | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1.57 | 0.25–10.06 | 0.6448 |
| CDH1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | n/a | ||
| RAD51C | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | n/a | ||
| RAD51D | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | n/a | ||
| BRIP1 | 1 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 5 | 2 | 3.95 | 0.85–19.9 | 0.1172 |
| BARD1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1.57 | 0.08–29.9 | >0.9999 |
| PTEN | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | n/a | ||
| Total PVs | 32 | 7 | 1 | 10 | 19 | 15 | 15 | 18 | 9 | 126 | 24 | |||
| Total tested | 487 | 66 | 63 | 53 | 108 | 59 | 37 | 33 | 12 | 918 | 1443 | |||
| % PVs | 6.6% | 10.6% | 1.6% | 18.9% | 17.6% | 25.4% | 40.5% | 54.5% | 75.0% | 13.7% | 1.7% | |||
| Total non-BRCA PVs | 26 | 6 | 0 | 6 | 6 | 8 | 3 | 2 | 0 | 57 | ||||
| % non-BRCA PVs | 5.3% | 9.1% | 0.0% | 11.3% | 5.6% | 13.6% | 8.1% | 6.1% | 0.0% | 6.2% | ||||
| % BRCA1/2 PVs | 1.2% | 1.5% | 1.6% | 7.5% | 12.0% | 11.9% | 32.4% | 48.5% | 75.0% | 7.5% | ||||
| % adjusted for all BRCA1/2 tested | 5.3% | 8.8% | 0.0% | 10.6% | 5.0% | 10.4% | 5.5% | 2.6% | 0.0% | 5.3% | ||||
| Negative pre-screen | ||||||||||||||
| ATM | 1 | 0 | 1 | 0 | 4 | 2 | 2 | 2 | 0 | 12 | 5 | 7.4 | 2.7–19.0 | <0.0001 |
| CHEK2 | 0 | 0 | 1 | 2 | 4 | 2 | 0 | 2 | 1 | 12 | 3 | 12.3 | 3.5–41.0 | <0.0001 |
| TP53 * | 1 | 0 | 0 | 0 | 4 | 1 | 1 | 0 | 1 | 8 | 0 | 84.7 | 13.2–941.5 | <0.0001 |
| PALB2 | 0 | 0 | 3 | 1 | 3 | 3 | 1 | 0 | 0 | 11 | 3 | 11.3 | 3.5–37.9 | <0.0001 |
| NBN | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 2 | 1.50 | 0.1–12.9 | 0.5777 |
| CDH1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | n/a | ||
| RAD51C | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | n/a | ||
| RAD51D | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | n/a | ||
| BRIP1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 | 2 | 3.02 | 0.5–19.3 | 0.261 |
| BARD1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | n/a | ||
| PTEN | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | n/a | ||
| Total PVs | 2 | 0 | 5 | 3 | 17 | 9 | 6 | 4 | 2 | 48 | 16 | |||
| Total tested | 38 | 12 | 28 | 53 | 147 | 90 | 58 | 39 | 15 | 480 | 1443 | |||
| % PVs | 5.3% | 0.0% | 17.9% | 5.7% | 11.6% | 10.0% | 10.3% | 10.3% | 13.3% | 10.0% | 1.1% | |||
| % adjusted for all BRCA1/2 tested | 5.2% | 0.0% | 17.1% | 5.3% | 10.3% | 7.7% | 7.0% | 4.5% | 2.8% | 8.5% | ||||
| All samples tested for BRCA1/2 | ||||||||||||||
| BRCA1 | 4 | 5 | 5 | 16 | 49 | 87 | 60 | 94 | 67 | 387 | ||||
| BRCA2 | 9 | 7 | 15 | 22 | 82 | 86 | 66 | 65 | 25 | 377 | ||||
| Total tested | 878 | 326 | 468 | 619 | 1240 | 745 | 387 | 281 | 116 | 5060 | ||||
| % BRCA1/2 PVs | 1.5% | 3.7% | 4.3% | 6.1% | 10.6% | 23.2% | 32.6% | 56.6% | 79.3% | 15.1% | ||||
* Population frequency estimate for local population taken as 1 in 5000; NA-Not assessable as 480 pre-screened for BRCA1/2.