Putative disease variants of low penetrance/tentative ALS genes
| Gene | Variant | SIFT | PolyPhen | Model | fALS | sALS | IRL | EUR | GLO |
|---|---|---|---|---|---|---|---|---|---|
| CHMP2B | c.118A>G(p.[Lys40Glu]) | Deleterious | Possibly damaging | D | 0/50 | 1/373 | 0/261 | NR | NR |
| CHMP2B | c.123G>T(p.[Gln41His]) | Deleterious | Possibly damaging | D | 0/50 | 1/373 | 0/263 | NR | NR |
| DCTN1 | c.2887-2A>G(p.?) | – | – | D | 0/39 | 2/239 | 0/246 | NR | NR |
| DPP6 | c.883G>A(p.[Glu295Lys]) | Deleterious | Probably damaging | D | 0/50 | 1/390 | 0/296 | NR | NR |
| ELP3 | c.206G>T(p.[Arg69Leu]) | Deleterious | Benign | D | 0/50 | 1/381 | 0/294 | NR | NR |
| ELP3 | c.326G>A(p.[Cys109Tyr]) | Deleterious | Probably damaging | D | 1/50 | 1/390 | 0/278 | 1/4578 | 1/6781 |
| FGGY | c.1716G>A(p.[Met572Ile]) | Tolerated | Possibly damaging | D | 0/48 | 1/376 | 0/285 | NR | NR |
| HFE | c.766G>A(p.[Val256Ile]) | Tolerated | Benign | D | 0/50 | 1/388 | 0/295 | NR | NR |
| ITPR2 | c.3614G>A(p.[Arg1205Gln]) | Tolerated | Probably damaging | D | 0/50 | 1/371 | 0/266 | NR | NR |
| MAPT | c.284C>T(p.[Thr95Met]) | Tolerated | Benign | D | 0/10 | 1/50 | 0/50 | 1/4349 | 1/6549 |
| MAPT | c.698C>T(p.[Pro233Leu]) | Tolerated | Probably damaging | D | 0/14 | 1/79 | 0/80 | NR | NR |
| PON2 | c.661T>G(p.[Ser221Ala]) | Tolerated | Benign | D | 0/49 | 1/381 | 0/257 | NR | NR |
| SPG11* | c.7324G>C(p.[Ala2442Pro]) | Deleterious | Probably damaging | D | 0/50 | 1/391 | 0/282 | NR | NR |
| SPG11* | c.4343G>A(p.[Cys1448Tyr]) | Deleterious | Possibly damaging | D | 0/50 | 1/388 | 0/300 | NR | NR |
| SPG11* | c.3680A>G(p.[Lys1227Arg]) | Tolerated | Benign | D | 1/50 | 0/390 | 0/302 | NR | NR |
| SPG11* | c.2577A>C(p.[Gln859His]) | Tolerated | Benign | D | 0/50 | 1/380 | 0/267 | NR | NR |
| SPG11* | c.1930A>T(p.[Thr644Ser]) | Tolerated | Benign | D | 1/49 | 0/382 | 0/265 | NR | NR |
| SPG11* | c.1529G>A(p.[Ser510Asn]) | Tolerated | Probably damaging | D | 0/50 | 1/389 | 0/282 | NR | NR |
| SPG11* | c.394A>G(p.[Ser132Gly]) | Tolerated | Benign | D | 0/50 | 1/391 | 0/279 | NR | NR |
| UNC13A | c.3098T>A(p.[Val1033Asp]) | Tolerated | Benign | D | 0/49 | 1/372 | 0/286 | NR | NR |
D—Variant may cause disease in a dominant fashion and carrier frequencies relate to heterozygote carriers.
NR—Variant not reported within either the 1000 genomes or ESP6500 datasets (samples of European ancestry=4679, total number of samples=7595).
CHMP2B—ENST00000263780; DCTN1—ENST00000361874; DPP6—ENST00000377770; ELP3—ENST00000256398; FGGY—ENST00000371218; HFE—ENST00000357618; ITPR2—ENST00000381340; MAPT—ENST00000344290; PON2—ENST00000222572; SPG11—ENST00000261866; UNC13A—ENST00000519716.
*Gene conventionally associated with recessively inherited ALS.
ALS, amyotrophic lateral sclerosis; ESP, Exome Sequencing Project.