Table 4. Candidate variants in early-onset breast cancer patients.
| Gene | Variant | N in cases (sample id) | Pathway or function | Cosmic db search tissue distribution |
|---|---|---|---|---|
| AKAP13 | c.571G>A, p.(G191R) | 1 (235004) | G Protein signalling | — |
| AKAP8 | c.1513A>G, p.(N505D) | 1 (236055) | G Protein signalling | — |
| APEX1 | c.190A>G, p.(I64V)a | 1 (110001) | TSH signalling, base excision repair | — |
| BIRC6 | c.2675A>G, p.(E892G) | 1 (110001) | Ubiquitin-mediated proteolysis, apoptosis modulation and signalling | — |
| BNIPL | c.33dupA, p.(T11fs)a | 1 (236055) | Interacts with BCL2, promotes cell death | — |
| BRCA1 | c.3155C>T, p.(P1052L) | 1 (904001) | Ubiquitin-mediated proteolysis, DNA damage response | — |
| CDC45 | c.326A>G, p.(E109G) | 1 (236055) | DNA replication, cell cycle | — |
| CDKN2B | c.56C>A, p.(A19D) | 1 (236055) | Cell cycle, TGF beta signalling, pathways in cancer | Hematopoietic and lymphoid |
| CHEK2 | c.470T>C, p.(I157T) | 1 (110010) | DNA damage response, p53 signalling, cell cycle | — |
| CINP | c.159C>G, p.(N53K) | 2 (260075, 913001) | DNA replication, checkpoint signalling | — |
| COL11A2 | c.32T>A, p.(L11H) | 1 (110010) | ECM-receptor interaction, focal adhesion | — |
| COL4A6 | c.3481A>G, p.(I1161V) | 1 (110010) | ECM-receptor interaction, pathways in cancer, focal adhesion | — |
| COL6A2 | c.679G>A, p.(D227N) | 1 (260075) | ECM-receptor interaction, focal adhesion | — |
| DENND2D | c.46C>T, p.(R16*) | 1 (904001) | Promotes the exchange of GDP to GTP | — |
| DHH | c.25C>G, p.(P9A) | 1 (260075) | Hedgehog signalling | — |
| DTX4 | c.1243C>T, p.(R415C) | 1 (235004) | Notch signalling | — |
| EDN3 | c.560dupA, p.(E187fs)a | 1 (110010) | Variety of cellular roles including proliferation, migration, differentiation | — |
| EFCAB13 | c.1009A>T, p.(K337*) | 1 (260075) | Calcium ion binding | — |
| EXO1 | c.836A>G, p.(N279S) | 1 (913001) | Mismatch repair | — |
| FANCD2 | c.2702G>T, p.(G901V) | 1 (235004) | DNA damage response | — |
| FBXW8 | c.1409C>T, p.(T470M) | 1 (913001) | Ubiquitin-mediated proteolysis | — |
| FOCAD | c.5047G>A, p.(A1683T) | 2 (110010, 904001) | Tumour suppressor in glioma and colorectal cancer | — |
| LAMA1 | c.2186G>A, p.(R729H) | 1 (913001) | ECM-receptor interaction, pathways in cancer, focal adhesion | Ovary |
| LAMA5 | c.5035C>T, p.(R1679W) | 2 (236005, 260075) | ECM-receptor interaction, pathways in cancer, focal adhesion | Pancreas and biliary tract |
| LAMA5 | c.3062C>T, p.(A1021V) | 1 (913001) | ECM-receptor interaction, pathways in cancer, focal adhesion | — |
| LAMA5 | c.7367G>A, p.(R2456H) | 1 (235004) | ECM-receptor interaction, pathways in cancer, focal adhesion | — |
| LAMA5 | c.6413G>T, p.(S2138I) | 1 (913001) | ECM-receptor interaction, pathways in cancer, focal adhesion | — |
| LAMB1 | c.2869G>A, p.(D957N) | 1 (260075) | ECM-receptor interaction, pathways in cancer, focal adhesion | — |
| LAMB2 | c.1306G>A, p.(G436S) | 1 (235004) | ECM-receptor interaction, pathways in cancer, focal adhesion | — |
| LAMC3 | c.1687C>T, p.(R563W) | 1 (235004) | ECM-receptor interaction, pathways in cancer, focal adhesion | Central nervous system |
| LIG1 | c.841G>A, p.(V281M) | 1 (904001) | DNA replication, mismatch repair, base and nucleotide excision repair | — |
| LRP2 | c.6850A>G, p.(T2284A) | 1 (913001) | Hedgehog signalling | — |
| LRP2 | c.5107C>T, p.(P1703S) | 1 (235004) | Hedgehog signalling | — |
| MAD1L1 | c.175C>T, p.(R59C) | 1 (913001) | Cell cycle, progesterone-mediated oocyte maturation | — |
| MAGEF1 | c.52dupG, p.(E18fs)a | 1 (110010) | Enhancer of ubiquitin ligase activity | Large intestine |
| MAP3K4 | c.2717A>C, p.(H906P) | 1 (904001) | DNA damage response, MAPK signalling | — |
| MBD4 | c.1073T>C, p.(I358T) | 1 (236005) | Base excision repair | — |
| NEIL3 | c.516G>C, p.(Q172H) | 1 (110010) | Base excision repair | — |
| NLRP4 | c.1912G>A, p.(G638R) | 1 (904001) | NOD signalling | — |
| NUMBL | c.1347T>G, p.(F449L) | 1 (235004) | Notch signalling | — |
| PLD1 | c.1192C>T, p.(R398C) | 2 (236055, 904001) | Glycerophospholipid metabolism, pathways in cancer | — |
| PRDM1 | c.1739C>T, p.(P580L) | 1 (235004) | NOD signalling | — |
| RASGRP3 | c.844G>A, p.(G282S) | 1 (236055) | Integrated cancer, MAPK signalling | — |
| RBL2 | c.98A>C, p.(D33A) | 2 (260075, 904001) | DNA damage response, TGF beta signalling, cell cycle | — |
| RBL2 | c.100G>C, p.(A34P) | 2 (904001, 913001) | DNA damage response, TGF beta signalling, cell cycle | — |
| RBL2 | c.179A>G, p.(E60G) | 1 (110010) | DNA damage response, TGF beta signalling, cell cycle | — |
| RET | c.2876G>A, p.(R959Q) | 1 (235004) | Pathways in cancer | Large intestine |
| RICTOR | c.3221A>G, p.(D1074G) | 1 (235004) | TOR signalling, mTOR signalling | — |
| S1PR5 | c.953T>A, p.(L318Q) | 2 (235004, 913001) | Signal transduction of S1P receptor | — |
| SOX17 | c.83G>T, p.(G28V) | 1 (235004) | Wnt signalling | — |
| TAB3 | c.743C>T, p.(T248M) | 1 (236055) | NOD-like receptor signalling | Large intestine |
| TICRR | c.1993C>T, p.(R665*) | 1 (260075) | DNA replication | — |
| TNC | c.1642G>A, p.(V548M) | 1 (110010) | ECM-receptor interaction, focal adhesion | — |
| TNC | c.2977G>C, p.(V993L) | 1 (913001) | ECM-receptor interaction, focal adhesion | — |
| UBE2Q1 | c.727A>C, p.(N243H) | 1 (235004) | Ubiquitin-mediated proteolysis | — |
| UBE3A | c.532G>A, p.(A178T) | 1 (913001) | Ubiquitin-mediated proteolysis | — |
Reference sequences: AKAP8:NM_005858.3; AKAP13:NM_006738.5; APEX1:NM_001244249.1; BIRC6:NM_016252.3; BNIPL:NM_138278.3; BRCA1:NM_007297.3; CDC45:NM_001178011.2; CDKN2B:NM_004936.3; CHEK2:NM_007194.3; CINP:NM_032630.2; COL4A6:NM_001287759.1; COL6A2:NM_001849.3; COL11A2:NM_001163771.1; DENND2D:NM_024901.4; DHH:NM_021044.2; DTX4:NM_015177.1; EDN3:NM_207032.2; EFCAB13:NM_001195192.1; EPSTI1:NM_001002264.2; EXO1:NM_003686.4; FANCD2:NM_001018115.2; FBXW8:NM_012174.1; FOCAD:NM_017794.4; LAMA1:NM_005559.3; LAMA5:NM_005560.4; LAMB1:NM_002291.2; LAMB2:NM_002292.3; LAMC3:NM_006059.3; LIG1:NM_001289064.1; LRP2:NM_004525.2; MAD1L1:NM_001013836.1; MAGEF1:NM_022149.4; MAP3K4:NM_005922.3; MBD4:NM_001276270.1; NEIL3:NM_018248.2; NLRP4:NM_134444.4; NUMBL:NM_001289979.1; PLD1:NM_001130081.2; PRDM1:NM_182907.2; RASGRP3:NM_015376.2; RBL2:NM_005611.3; RET:NM_020630.4; RICTOR:NM_001285439.1; SOX17:NM_022454.3; S1PR5:NM_001166215.1; TAB3:NM_152787.4; TICRR:NM_152259.3; TNC:NM_002160.3; UBE2Q1:NM_017582.6; UBE3A:NM_130838.1.
a
Segregation was further studied in the family.