Table 2.
Rare protein truncating variants in the BROCA gene set
| Gene | dbSNP ID | Variant type | Ref | Alt | Protein change | ClinVar | ExAC MAF (EUR) | CADD | Phenotype category |
|---|---|---|---|---|---|---|---|---|---|
| ATM | Frameshift deletion | A | – | p.K828fs | – | – | 31 | Non-aggressive | |
| ATM | rs587779834 | Frameshift deletion | G | – | p.V1268fs | 5 | 4.5×10−5 | 28.3 | Metastatic |
| ATM | rs786204751 | Nonsense | C | T | p.Q1839* | 4 | – | 46 | Metastatic |
| ATM | rs770641163 | Nonsense | C | T | p.R2993* | 5|4 | 3.0×10−5 | 47 | Metastatic |
| ATR | Nonsense | A | T | p.Y1527* | – | – | 42 | Metastatic | |
| BRCA2 | rs41293477 | Nonsense | T | G | p.L1053* | 5 | – | 29.2 | Non-aggressive |
| BRCA2 | rs80359454 | Frameshift deletion | GAAA | – | p.E1493fs | 5 | – | 29.6 | Metastatic |
| BRCA2 | rs80359470 | Frameshift deletion | AA | – | p.N1626fs | 5 | – | 25.5 | Metastatic |
| BRCA2 | rs11571658 | Frameshift deletion | TT | – | p.L2092fs | 5 | 1.5×10−5 | 24.6 | Metastatic |
| BRCA2 | rs80359752 | Frameshift insertion | – | A | p.T3085fs | 5 | – | 36 | Metastatic |
| CHEK2 | rs587781269 | Nonsense | G | A | p.R95* | 5 | 0 | 38 | Non-aggressive |
| NBN | rs587780100 | Frameshift deletion | TGTT | – | p.K233fs | 5 | 4.7×10−5 | 35 | Metastatic |
| NBN | rs587776650 | Frameshift deletion | TTTGT | – | p.K219fs | 5 | 3.2×10−5 | 35 | Metastatic |
| NBN | Frameshift deletion | C | – | p.R89fs | – | – | 8.3 | Metastatic | |
| NBN | rs587781891 | Frameshift deletion | G | – | p.I41fs | 5 | – | 28.3 | Metastatic |
| PALB2 | rs180177110 | Nonsense | G | A | p.R753* | 5 | 4.5×10−5 | 35 | Metastatic |
| PMS2 | Nonsense | G | A | p.Q244* | – | – | 40 | Metastatic | |
| PRSS1 | rs766199324 | Frameshift deletion | C | – | p.P164fs | – | 1.5×10−5 | 26 | Metastatic |
| RAD51D | rs786202750 | Frameshift deletion | A | – | p.T188fs | 5 | – | 27 | Metastatic |
| SLX4 | Frameshift deletion | C | – | p.A1653fs | – | – | 20.5 | Non-aggressive | |
| SLX4 | rs767631456 | Frameshift deletion | CT | – | p.S936fs | – | 4.5×10−5 | 24 | Metastatic |
| XRCC2 | rs776336749 | Frameshift deletion | T | – | p.H268fs | 3 | 0 | 28.3 | Metastatic |
All Tier 1 variants identified for genes in the 60 gene BROCA panel are described, alongside case phenotype status. For each variant, the type of alteration, consequence at the protein level and CADD score are provided. dbSNP identifiers, ClinVar clinical significance score (5 = pathogenic, 4 = likely pathogenic, 3 = uncertain significance) and minor allele frequency in ExAC non-Finnish Europeans are provided for variants present in the respective databases