Table 10. .
Identified FANCD2 Mutations and Their Effects
| Mutationa |
Consequencea |
||
| Location and Patient No(s). | Genomic DNA | RNA | Protein |
| Exon 2: | |||
| 32 | c.2T→C | r.2T→C | Failure of normal translation initiation |
| Intron 3: | |||
| 28 and 29 | c.206-2A→T (IVS3-2 A→T) | r.206_273del68 (exon 4 skipping) | p.A69DfsX7 |
| Intron 4: | |||
| 6, 12, and 30 | c.274-57_-56insinvAluYb8nt36_319 +dup c.274-69_−57b | r.274_377del104 (exon 5 skipping) | p.I92YfsX7 |
| Exon 5: | |||
| 26 and 27 | c.376A→G | r.376A→G+r.377_378ins13 (aberrant splicing) | p.S126RfsX12 |
| Exon 9: | |||
| 19 | c.692T→G | r.692T→G | p.L231R |
| Intron 9: | |||
| 1 | c.696-121C→G (IVS9-12 1C→G) | r.695+1619_696-126ins34 (exonization) | p.S232insQNNFX |
| 18 | c.696-2A→T (IVS9-2 A→T) | r.696_783del88 (exon 10 skipping) | p.S232RfsX6 |
| Exon 10: | |||
| 23 and 24 | c.757C→T | r.757C→T | p.R253X |
| 31 and 33 | c.782A→T | r.696_783del88 (exon 10 skipping) | p.S232RfsX6 |
| Exon 11: | |||
| 9 | c.810_812delGTC | r.810_812delGTC | p.S271del |
| Exon 12: | |||
| 7 | c.904C→T | r.904C→T | p.R302W |
| Intron 12: | |||
| 8 | c.990-1G→A (IVS12-1 G→A) | r.990del8 (aberrant splicing) | p.S330RfsX16 |
| Exon 13: | |||
| 7 | c.1092G→A | r.1092G→A | p.W364X |
| Intron 14: | |||
| 33 | g.13377_17458dup4082 (duplication, including exons 11–14) | r.784_1134dup (duplication of 351 nt in-frame) | p.262_378dup (duplication of 117 aa) |
| Exon 16: | |||
| 18 | c.1321_1322delAG | r.1135_1545del411 (exon 15–17 skipping) | p.V379_K515del |
| 23 and 24 | c.1367T→G | r.1367T→G | p.L456R |
| 31 | c.1370T→C | r.1370T→C | p.L457P |
| Exon 17: | |||
| 28, 29 | g.22875_23333del459 (c.1414-71_c.1545+256del459) | r.1414_1545del132 | p.E472_K515del |
| Intron 21: | |||
| 3, 4, 5, 9, 10, 13, and 25 | c.1948-16T→G (IVS21-16 T→G) | r.1948_2021del74 (exon 22 skipping) | p.E650X |
| 2, 8, 14, 15, and 20 | c.1948-6C→A (IVS21-6 C→A) | r.1948_2021del74 (exon 22 skipping) | p.E650X |
| Exon 26: | |||
| 21 | c.2404C→T | r.2404C→T | p.Q802X |
| 16, 17, 19, 21, 22, and 30 | c.2444G→A | r.2444G→A | p.R815Q |
| Exon 28: | |||
| 20 | c.2660delA | r.2660delA | p.E888RfsX16 |
| Intron 28: | |||
| 10 and 22 | c.2715+1G→A (IVS28+1G→A) | r.2715_2716ins27 (aberrant splicing) | p.E906LfsX4 |
| Exon 29: | |||
| 14 and 15 | c. 2775_2776CC→TT | r. 2775_2776CC→TT | p.R926X |
| 11 | c.2835dupC | r.2835dupC | p.D947RfsX3 |
| Exon 34: | |||
| 12 | c.3453_3456delCAAA | r.3453_3456delCAAA | p.N1151KfsX46 |
| Exon 36: | |||
| 2 | c.3599delT | r.3599delT | p.I1200KfsX12 |
| Exon 37: | |||
| 32 | c.3706C→A | r.3684_3707del24 (aberrant splicing) | p.R1228S_F1235del |
| 11 | c.3707G→A | r.3684_3727del44 (aberrant splicing) | p.H1229EfsX7 |
| Exon 38: | |||
| 6, 26, and 27 | c.3803G→A | r.3803G→A | p.W1268X |
a
Nomenclature is according to the Human Genome Variation Society.
b
This Alu was identical to the evolutionary young subfamily Yb8.43,44 It was lacking its annotated nucleotides 1–35, had integrated in reverse orientation (with its poly-A tail toward the 5′ end of FANCD2), and had duplicated the 13-nt sequence c.274–69 to c.274–57 of FANCD2 IVS4, such that this duplicated sequence flanked the Alu repeat on both sides. Altogether, the insertion length was 298 bp.