From: CHEK2 contribution to hereditary breast cancer in non-BRCAfamilies
Mutation | Amino acid change | Exon | Protein domain | Splicing effect | Align-GVGD class | SIFT median sequence conservation score | SIFT prediction | PolyPhen-2 prediction | Proposed diagnosis |
---|---|---|---|---|---|---|---|---|---|
Case population (n = 13) | Â | Â | Â | Â | Â | Â | Â | Â | Â |
190G > A [49] (two cases) | Glu64Lys | 2 | SQ/TQ | - | C15 | 2.23 | Tolerated | Benign | Probably benign |
190G > T | Glu64X | 2 | SQ/TQ | - | - | Â | - | - | Probably deleterious |
Pro85Arg | 2 | - | - | C0 | 2.15 | Tolerated | Probably damaging | Probably deleterious | |
349A > G [23] | Arg117Gly | 3 | FHA | - | C65 | 2.07 | Deleterious | Probably damaging | Probably deleterious |
670A > G | Lys224Glu | 5 | Kinase | - | C0 | 2.05 | Tolerated | Benign | Probably benign |
731A > G | Lys244Arg | 6 | Kinase | - | C0 | 2.04 | Tolerated | Benign | Probably benign |
751A > T [23] | Ile251Phe | 6 | Kinase | - | C0 | 2.04 | Tolerated | Probably damaging | Probably deleterious |
846+4_846+7del | - | 7 | - | Possibly skip exon 7 | - | - | - | - | Probably deleterious |
1100del (three cases) | Thr367MetfsX15 | 11 | Kinase | - | - | - | - | - | Probably deleterious |
1169A > C | Tyr390Ser | 11 | Kinase | - | C0 | 2.04 | Deleterious | Probably damaging | Probably deleterious |
1281C > A | Phe427Leu | 12 | Kinase | - | C0 | 2.04 | Deleterious | Probably damaging | Probably deleterious |
1427C > T [23] | Thr476Met | 13 | Kinase | - | C0 | 2.05 | Deleterious | Probably damaging | Probably deleterious |
Control population (n = 4) | Â | Â | Â | Â | Â | Â | Â | Â | Â |
116C > T | Ser39Phe | 2 | SQ/TQ | - | C65 | 3.10 | Deleterious | Benign | Probably deleterious |
251A > G | Glu84Gly | 2 | - | - | C65 | 2.17 | Tolerated | Probably damaging | Probably deleterious |
731A > G | Lys244Arg | 6 | Kinase | - | C0 | 2.04 | Tolerated | Benign | Probably benign |
792+1dup | - | 6 | - | Probably skip exon 6 | - | - | - | - | Probably deleterious |
Additional mutations tested for kinase function [27] | Â | Â | Â | Â | Â | ||||
410G > A | Arg137Gln | 3 | FHA | - | C0 | 2.22 | Tolerated | Benign | Probably benign |
433C > T | Arg145Trp | 3 | FHA | - | C65 | 2.05 | Tolerated | Probably damaging | Probably deleterious |
481_483del | Glu161del | 4 | FHA | - | - | - | - | - | Probably deleterious |
539G > A | Arg180His | 4 | FHA | - | C0 | 2.04 | Tolerated | Probably damaging | Probably deleterious |