Genes and mutations identified in 27 FA families by next-generation sequencing technologies and aCGH
| . | . | Mutation 1 (maternal) . | Mutation 2 (paternal) . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample ID . | Gene . | Exon-intron . | Nucleotide (hg18) . | cDNA . | Protein . | Comments . | Exon-intron . | Nucleotide (hg18) . | cDNA . | Protein . | Comments . |
| MIP-targeted capture | |||||||||||
| FA1 | FANCA | 16 | chr16:88376916 | c.1566G>A | p.K522K | Novel, skips exon 16 | 16-17 | del chr16:88374749-88377749† | — | — | — |
| FA2 | FANCB | 9 | chrX:14772684 | c.2027T>C | p.L676P | De novo, novel, subsequently complemented by FANCB | — | — | — | — | — |
| FA3 | FANCB | 9 | chrX:14772652 | c.2059G>T | p.E687* | Novel | — | — | — | — | — |
| FA4 | FANCC | 2 | chr9:97051386-97051387 | c.8_9delAA | p.Q3Rfs*7 | Novel | 2 | chr9:97051386-97051387 | c.8_9delAA | p.Q3Rfs*7 | Novel |
| FA5 | FANCD1 | 11 | chr13:31809756 | c.3264dupT | p.P1088Pfs*15 | — | 19i | chr13:31842697 | c.8487+3A>G | — | — |
| FA6 | FANCF | 1 | chr11:22603448- 22603453 | c.480_485delCT | p.L162Dfs*102 | — | 1 | chr11:22603448-22603453 | c.480_485delCT | p.L162Dfs*102 | — |
| FA7 | FANCG | 10 | chr9:35065742 | c.1153C>A | p.P385T | De novo, novel | 13 | chr9:35064381 | c.1747G>T | p.E583* | Novel, skips exon 13 |
| FA8 | FANCJ | 17 | chr17:57148196 | c.2390A>G | p.K797R | Novel | 17 | chr17:57148194 | c.2392C>T | p.R798* | — |
| FA9 | FANCA | 20i | chr16:88369725 | c.1827-1G>A | — | — | 36 | chr16:88338972-88338977 | c.3520_3522delTGG | p.W1174del | — |
| FA10 | FANCC | 1‡ | del chr9:97116249-97124749† | — | — | Novel, RNA not expressed | 5i | chr9:96974136 | c.456+4A>T | — | — |
| FA11 | FANCB | 2 | dup chrX:14788000-14797000† | — | — | Novel | — | — | — | — | — |
| FA12 | FANCG | 10 | chr9:35065737-35065742 | c.1158dupC | p.S387Lfs*8 | Novel | 8 | chr9:35066497 | c.1008dupA | p.P337Tfs*40 | — |
| FA13 | FANCL | 5i | chr2:58286898† | c.375-2033C>G | — | Novel, skips exons 4, 6, and 7 | 12 | chr2:58242172-58242174 | c.1007_1009delTAT | p.I336-C337delinsS | — |
| FA14 | FANCI | 13 | chr15:87621097 | c.1264G>A | p.G422R | — | 16i | chr15:87626212† | c.1583+142C>T | — | Novel, inserts part of intron 16 |
| FA15 | FANCJ | 7 | chr17:57240777 | c.751C>T | p.R251C | — | 9 | chr17:57231397 | c.1186C>G | p.H396D | — |
| FA16 | FANCF | 1 | chr11:22603448-22603453 | c.480_485delCT | p.L162Dfs*102 | — | 1 | chr11:22603448-22603453 | c.480_485delCT | p.L162Dfs*102 | — |
| FA17 | FANCL | 13 | chr2:58240747† | c.1092G>A | p.K364K | Novel, skips exon13 | 13 | chr2:58240747 | c.1092G>A | p.K364K | Novel, skips exon13 |
| MIP-targeted capture and WES | |||||||||||
| FA18 | FANCD2 | 15i | chr3:10063413 | c.1278+6T>C§ | — | Novel | 18 | del chr3:10066949-10071649† | — | — | — |
| FA19 | FANCD2 | 16 | chr3:10064601† | c.1279G>T | p.V427F | Novel, skips exon16 | 7i | chr3:10053024 | c.491+1G>A§ | — | Novel |
| TruSeq-targeted capture | |||||||||||
| FA20 | FANCA | 39 | chr16:88333953 | c.3884T>G | p.L1295* | — | 37-43|| | del chr16:88172538-88337600† | — | — | — |
| FA21 | FANCD2 | 12i | chr3:10060167 | c.990-1G>A | — | — | 38 | chr3:10108889 | c.3802T>G | p.W1268G | Novel |
| FA22 | FANCA | 14 | chr16:88385367 | c.1304G>T | p.R435L | Novel | 20i | chr16:88369725 | c.1827-1G>A | — | |
| FA23 | FANCA | 33i | chr16:88342567 | c.3348+1G>A | — | — | 36 | chr16:88338972-88338978 | c.3520_3522delTGG | p.W1174del | — |
| FA24 | FANCA | 13 | chr16:88385943-88385946 | c.1115_1118delTTGG | p.V372Afs*42 | — | 15 | chr16:88378855 | c.1378C>T | p.R460* | Novel |
| FA25 | FANCC | 2 | chr9:97051328-97051330 | c.67delG | p.D23Ifs*23 | — | 7 | chr9:96952159 | c.553C>T | p.R185* | — |
| FA26 | FANCL | 5i | chr2:58286898† | c.375-2033C>G | — | Novel, multiple splicing aberrations¶ | 11 | chr2:58243534-58243540 | c.871_874delGATT | p.D291Ffs*49 | Novel |
| FA27 | FANCA | 20i | chr16:88369725 | c.1827-1G>A | — | — | 1-5# | del chr16:88403999-88437249† | — | — | — |
| . | . | Mutation 1 (maternal) . | Mutation 2 (paternal) . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample ID . | Gene . | Exon-intron . | Nucleotide (hg18) . | cDNA . | Protein . | Comments . | Exon-intron . | Nucleotide (hg18) . | cDNA . | Protein . | Comments . |
| MIP-targeted capture | |||||||||||
| FA1 | FANCA | 16 | chr16:88376916 | c.1566G>A | p.K522K | Novel, skips exon 16 | 16-17 | del chr16:88374749-88377749† | — | — | — |
| FA2 | FANCB | 9 | chrX:14772684 | c.2027T>C | p.L676P | De novo, novel, subsequently complemented by FANCB | — | — | — | — | — |
| FA3 | FANCB | 9 | chrX:14772652 | c.2059G>T | p.E687* | Novel | — | — | — | — | — |
| FA4 | FANCC | 2 | chr9:97051386-97051387 | c.8_9delAA | p.Q3Rfs*7 | Novel | 2 | chr9:97051386-97051387 | c.8_9delAA | p.Q3Rfs*7 | Novel |
| FA5 | FANCD1 | 11 | chr13:31809756 | c.3264dupT | p.P1088Pfs*15 | — | 19i | chr13:31842697 | c.8487+3A>G | — | — |
| FA6 | FANCF | 1 | chr11:22603448- 22603453 | c.480_485delCT | p.L162Dfs*102 | — | 1 | chr11:22603448-22603453 | c.480_485delCT | p.L162Dfs*102 | — |
| FA7 | FANCG | 10 | chr9:35065742 | c.1153C>A | p.P385T | De novo, novel | 13 | chr9:35064381 | c.1747G>T | p.E583* | Novel, skips exon 13 |
| FA8 | FANCJ | 17 | chr17:57148196 | c.2390A>G | p.K797R | Novel | 17 | chr17:57148194 | c.2392C>T | p.R798* | — |
| FA9 | FANCA | 20i | chr16:88369725 | c.1827-1G>A | — | — | 36 | chr16:88338972-88338977 | c.3520_3522delTGG | p.W1174del | — |
| FA10 | FANCC | 1‡ | del chr9:97116249-97124749† | — | — | Novel, RNA not expressed | 5i | chr9:96974136 | c.456+4A>T | — | — |
| FA11 | FANCB | 2 | dup chrX:14788000-14797000† | — | — | Novel | — | — | — | — | — |
| FA12 | FANCG | 10 | chr9:35065737-35065742 | c.1158dupC | p.S387Lfs*8 | Novel | 8 | chr9:35066497 | c.1008dupA | p.P337Tfs*40 | — |
| FA13 | FANCL | 5i | chr2:58286898† | c.375-2033C>G | — | Novel, skips exons 4, 6, and 7 | 12 | chr2:58242172-58242174 | c.1007_1009delTAT | p.I336-C337delinsS | — |
| FA14 | FANCI | 13 | chr15:87621097 | c.1264G>A | p.G422R | — | 16i | chr15:87626212† | c.1583+142C>T | — | Novel, inserts part of intron 16 |
| FA15 | FANCJ | 7 | chr17:57240777 | c.751C>T | p.R251C | — | 9 | chr17:57231397 | c.1186C>G | p.H396D | — |
| FA16 | FANCF | 1 | chr11:22603448-22603453 | c.480_485delCT | p.L162Dfs*102 | — | 1 | chr11:22603448-22603453 | c.480_485delCT | p.L162Dfs*102 | — |
| FA17 | FANCL | 13 | chr2:58240747† | c.1092G>A | p.K364K | Novel, skips exon13 | 13 | chr2:58240747 | c.1092G>A | p.K364K | Novel, skips exon13 |
| MIP-targeted capture and WES | |||||||||||
| FA18 | FANCD2 | 15i | chr3:10063413 | c.1278+6T>C§ | — | Novel | 18 | del chr3:10066949-10071649† | — | — | — |
| FA19 | FANCD2 | 16 | chr3:10064601† | c.1279G>T | p.V427F | Novel, skips exon16 | 7i | chr3:10053024 | c.491+1G>A§ | — | Novel |
| TruSeq-targeted capture | |||||||||||
| FA20 | FANCA | 39 | chr16:88333953 | c.3884T>G | p.L1295* | — | 37-43|| | del chr16:88172538-88337600† | — | — | — |
| FA21 | FANCD2 | 12i | chr3:10060167 | c.990-1G>A | — | — | 38 | chr3:10108889 | c.3802T>G | p.W1268G | Novel |
| FA22 | FANCA | 14 | chr16:88385367 | c.1304G>T | p.R435L | Novel | 20i | chr16:88369725 | c.1827-1G>A | — | |
| FA23 | FANCA | 33i | chr16:88342567 | c.3348+1G>A | — | — | 36 | chr16:88338972-88338978 | c.3520_3522delTGG | p.W1174del | — |
| FA24 | FANCA | 13 | chr16:88385943-88385946 | c.1115_1118delTTGG | p.V372Afs*42 | — | 15 | chr16:88378855 | c.1378C>T | p.R460* | Novel |
| FA25 | FANCC | 2 | chr9:97051328-97051330 | c.67delG | p.D23Ifs*23 | — | 7 | chr9:96952159 | c.553C>T | p.R185* | — |
| FA26 | FANCL | 5i | chr2:58286898† | c.375-2033C>G | — | Novel, multiple splicing aberrations¶ | 11 | chr2:58243534-58243540 | c.871_874delGATT | p.D291Ffs*49 | Novel |
| FA27 | FANCA | 20i | chr16:88369725 | c.1827-1G>A | — | — | 1-5# | del chr16:88403999-88437249† | — | — | — |
All genomic coordinates refer to Build 36.1 (hg18). The mutation nomenclature is in accordance with the Human Genome Variation Society (http://www.hgvs.org/mutnomen/standards.html#aalist). Paternal DNA is unavailable for FA16, FA23, and FA25, and maternal DNA is unavailable for FA9. Both parental DNAs are unavailable for FA18, FA20, FA21, FA26, and FA27, and for these families, the assignment of the maternal and paternal mutations is arbitrary. FA2, FA3, and FA11 are male individuals belonging to the X-linked FANCB group and will have only 1 mutation. Pathogenicity prediction for p.R435L by SIFT (not tolerated), PolyPhen2 (probably damaging), and PANTHER (subPSEC, −5.18; Pdeleterious, 0.89). Pathogenicity prediction for p.K797R by SIFT (not tolerated), PolyPhen2 (probably damaging), and PANTHER (subPSEC, −3.85; Pdeleterious, 0.70). Pathogenicity prediction for p.W1268G by SIFT (not tolerated), PolyPhen2 (probably damaging), and PANTHER (subPSEC, −4.36; Pdeleterious, 0.80). Pathogenicity prediction for p.L676P by SIFT (not tolerated), PolyPhen2 (probably damaging), and PANTHER (not available). Pathogenicity prediction for p.P385T by SIFT (tolerated), PolyPhen2 (probably damaging), and PANTHER (subPSEC, −3.08087; Pdeleterious, 0.52).
cDNA, complementary DNA.
Indicates STOP condons in Protein columns.
Finding these pathogenic variants required aCGH and/or RNA-seq.
Plus 5 kb upstream.
From WES data.
Plus 160 kb downstream.
ins c.375-2034_2066, c.375-2300_2360, and skipping of exons 4, 6, and 7.
Plus 25 kb upstream.