Table 2

Putative disease variants of low penetrance/tentative ALS genes

GeneVariantSIFTPolyPhenModelfALSsALSIRLEURGLO
CHMP2Bc.118A>G(p.[Lys40Glu])DeleteriousPossibly damagingD0/501/3730/261NRNR
CHMP2Bc.123G>T(p.[Gln41His])DeleteriousPossibly damagingD0/501/3730/263NRNR
DCTN1c.2887-2A>G(p.?)D0/392/2390/246NRNR
DPP6c.883G>A(p.[Glu295Lys])DeleteriousProbably damagingD0/501/3900/296NRNR
ELP3c.206G>T(p.[Arg69Leu])DeleteriousBenignD0/501/3810/294NRNR
ELP3c.326G>A(p.[Cys109Tyr])DeleteriousProbably damagingD1/501/3900/2781/45781/6781
FGGYc.1716G>A(p.[Met572Ile])ToleratedPossibly damagingD0/481/3760/285NRNR
HFEc.766G>A(p.[Val256Ile])ToleratedBenignD0/501/3880/295NRNR
ITPR2c.3614G>A(p.[Arg1205Gln])ToleratedProbably damagingD0/501/3710/266NRNR
MAPTc.284C>T(p.[Thr95Met])ToleratedBenignD0/101/500/501/43491/6549
MAPTc.698C>T(p.[Pro233Leu])ToleratedProbably damagingD0/141/790/80NRNR
PON2c.661T>G(p.[Ser221Ala])ToleratedBenignD0/491/3810/257NRNR
SPG11*c.7324G>C(p.[Ala2442Pro])DeleteriousProbably damagingD0/501/3910/282NRNR
SPG11*c.4343G>A(p.[Cys1448Tyr])DeleteriousPossibly damagingD0/501/3880/300NRNR
SPG11*c.3680A>G(p.[Lys1227Arg])ToleratedBenignD1/500/3900/302NRNR
SPG11*c.2577A>C(p.[Gln859His])ToleratedBenignD0/501/3800/267NRNR
SPG11*c.1930A>T(p.[Thr644Ser])ToleratedBenignD1/490/3820/265NRNR
SPG11*c.1529G>A(p.[Ser510Asn])ToleratedProbably damagingD0/501/3890/282NRNR
SPG11*c.394A>G(p.[Ser132Gly])ToleratedBenignD0/501/3910/279NRNR
UNC13Ac.3098T>A(p.[Val1033Asp])ToleratedBenignD0/491/3720/286NRNR
  • 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.