Table 1. Variant frequencies.
| Carrier frequency | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Females | Males | |||||||||||
| Gene | Nucleotide change | Effect on protein | Rs-number | Frequency in ESP6500 | Affects function by prediction programmea | HBOC cases | Controls | BC cases | Controls | P-value | OR; 95%CI | Mutation loadb |
| AKT2 | c.148C>A | p.(P50T) | rs184042322 | 0.0127 | 3, 5 | 2/127 | 5/280 | — | — | 1 | 0.88; 0.17–4.57 | 3/1 |
| ATM | c.2572T>C | p.(F858L) | rs1800056 | 0.0090 | 1, 4, 5 | 1/129 | 10/975 | — | — | 1 | 0.75; 0.10–5.92 | |
| ATM | c.3161C>G | p.(P1054R) | rs1800057 | 0.0171 | 1, 2, 3, 4, 6 | 1/129 | 14/981 | — | — | 1 | 0.54; 0.07–4.13 | |
| ATM | c.4424A>G | p.(Y1475C) | rs34640941 | 0.0008 | 1, 2, 3 | 0/129 | 1/278 | 0/49 | 0/909 | 1/1c | na | 11/5 |
| ATM | c.5558A>T | p.(D1853V) | rs1801673 | 0.0048 | 1, 3, 4, 6 | 1/129 | 5/989 | — | — | 0.52 | 1.54; 0.18–13.19 | |
| BRCA1 | c.3904A>C | p.(T1302P) | rs80357231 | na | 7 | 0/128 | 0/986 | — | — | 1 | na | 11/6 |
| CDKN2A | c.496C>T | p.(H166Y) | rs181044510 | na | 6 | 3/129 | 7/280 | — | — | 1 | 0.93; 0.24–3.62 | 8/5 |
| MYC | c.77A>G | p.(N26S) | rs4645959 | 0.0289 | 1, 2, 3, 4, 5 | 5/129d | 23/987 | — | — | 0.14 | 2.02; 0.81–5.01 | 2/1 |
| NCOA3 | c.3353A>C | p.(Q1118P) | rs149561356 | 0.0007 | 3, 5 | 0/129 | 7/279 | — | — | 0.10 | na | 11/2 |
| PLAU | c.43G>T | p.(V15L) | rs2227580 | 0.0078 | 7 | 2/129 | 11/984 | — | — | 0.60 | 2.16; 0.30–15.45 | 3/1 |
| RAD1 | c.341G>A | p.(G114D) | rs2308957 | 0.0048 | 1, 2, 3, 4, 6 | 5/129 | 15/464 | — | — | 0.79 | 1.16; 0.42–3.22 | 3/2 |
| RAD50 | c.280A>C | p.(I94L) | rs28903085 | 0.0035 | 3 | 0/129 | 0/187 | 0/49 | 1/909 | 1/1c | na | 1/1 |
| RAD52 | c.538G>A | p.(G180R) | rs7487683 | 0.0246 | 1 | 4/129 | 15/269 | — | — | 0.33 | 0.55; 0.18–1.67 | 1/1 |
| RBL2 | c.1723G>C | p.(E575Q) | rs76818213 | 0.0156 | 1, 2, 3, 4, 5, 6, 7, 8, 9 | 8/129 | 22/261 | — | — | 0.55 | 0.73; 0.32–1.66 | 11/7 |
| RPA2 | c.122C>T | p.(S41F) | rs149249571 | 0.0004 | 6 | 0/129 | 5/467 | — | — | 0.59 | na | 1/1 |
| RRM2B | c.211dupC | p.(R71fs) | — | na | na | 16/128e | 22/247f | — | — | 0.31 | 1.39; 0.73–2.64 | 4/2 |
| WNT3A | c.277G>A | p.(D93N) | rs201274685 | 0.0003 | 1, 2, 3, 4, 6 | 1/129 | 4/468 | — | — | 1 | 0.91; 0.10–8.15 | 2/1 |
| WNT10A | c.337C>T | p.(R113C) | rs141074983 | na | 3 | 1/129 | 10/988 | — | — | 1 | 0.77; 0.10–6.00 | 1/1 |
Abbreviations: BC, breast cancer; CI, confidence interval; HBOC, hereditary breast and/or ovarian cancer; na, not available; OR, odds ratio. Reference sequences: AKT2, NM_001626.5; ATM, NM_000051.3; BRCA1, NM_007297.3; CDKN2A, NM_001195132.1; MYC, NM_002467.4; NCOA3, NM_001174087.1; PLAU, NM_002658.3; RAD1, NM_002853.3; RAD50, NM_005732.3; RAD52, NM_001297420.1; RBL2, NM_005611.3; RPA2, NM_001297558.1; RRM2B, NM_001172477.1; WNT3A, NM_033131.3 and WNT10A, NM_025216.2.
Prediction programmes: 1, Polyphen2_HDIV; 2, Polyphen2_HVAR; 3, MutationTaster; 4, MutationAssessor; 5, LRT; 6, SIFT; 7, FATHMM; 8, RadialSVM; 9, LR.
Total number of identified different variants in a gene/Predicted function-affecting variants identified in a gene.
Females/males.
Homozygous in 1/129 of the HBOC cases.
Homozygous in 1/128 of the HBOC cases.
Homozygous in 2/247 of the female controls.