Table 2 Interpretation of identified variants and their pathogenicity
Gene | Mutation | Function | Novel/known | SNP-ID | Mutation Tasting/SIFT/Provean/PolyPhen-2 | CADD score | Clinvar | GnomAD, ExAC, 1000 Genomes Frequency | ACMG | Publication (PMID) |
|---|---|---|---|---|---|---|---|---|---|---|
MAPT | NM_005910 p.Asn279Lys/c.837 T > G | Missense | Known | Rs63750756 | D/D/D/D | 26.5 | P | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 9,789,048 |
MAPT | NM_005910 p.Pro301Leu/c.902C > T | Missense | Known | Rs63751273 | D/D/D/D | 31 | P | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 9,641,683 |
MAPT | NM_005910 p.Val337Met/c.1009G > A | Missense | Known | Rs63750570 | D/D/D/D | 26.9 | P | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 9,629,852 |
MAPT | NM_005910 p.Asn296Asn/c.888T > C | Synonymous | Known | Rs63750912 | N/T/N/B | 0 | P | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 11,117,553 |
MAPT | NM_005910 p.Gln351Arg/c.1052A > G | Missense | Known | NA | D/D/N/P | 23.7 | LP | 0,0,0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 23,998,300 |
MAPT | NM_005910 p.Arg5Cys/c.13C > T | Missense | Known | Rs766166210 | D/D/D/P | 27.8 | VUS/B | 3/250984, 2/118630,0 | LP: PM1 + PM2 + PM5 + PP3 + PP4 | 25,604,855 |
MAPT | NM_005910 p.Arg5His/c.14G > A | Missense | Known | Rs63750959 | D/T/N/B | 22.9 | LB/VUS/P | 3/140076, 7/118676, 2/5008 | P: PS1 + PS3 + PM1 + PM5 + PP4 | 11,921,059 |
MAPT | NM_005910 p.Asp54Asn/c.160G > A | Missense | Novel | NA | N/D/N/D | 26.9 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
MAPT | NM_005910 p.Glu342Lys/c.1024G > A | Missense | Novel | NA | D/D/D/B | 23.5 | NA | 0,0,0 | LP: PM1 + PM2 + PM5 + PP3 + PP4 | NA |
MAPT | NM_005910 p.Ser285Arg/c.853A > C | Missense | Known | NA | D/D/D/D | 27.8 | NA | 0,0,0 | LP: PM1 + PM2 + PP1 + PP3 + PP4 | 25,443,551 |
MAPT | NM_005910 p.Arg221Pro/c.662G > C | Missense | Novel | NA | D/D/D/D | 25.5 | NA | 0,0,0 | LP: PM1 + PM2 + PM5 + PP3 + PP4 | NA |
MAPT | NM_005910 p.Gly389Arg/c.2341G > A | Missense | Known | Rs63750512 | D/D/D/D | 28.4 | P | 3/251208, 2/120720,0 | P: PS1 + PS4 + PM1 + PM2 + PP3 + PP4 | 11,117,542 |
MAPT | NM_005910 p.Thr263Ile/c.788C > T | Missense | Novel | NA | D/D/D/D | 24.2 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
TBK1 | NM_013254 p.Glu696Gly/c.2087A > G | Missense | Novel | NA | D/T/D/P | 29.3 | NA | 0,0,0 | P: PS3 + PM2 + PM5 + PP3 + PP4 | NA |
TBK1 | NM_013254 p.Ile37Thr/c.110T > C | Missense | Novel | NA | D/D/D/B | 23.6 | NA | 0,0,0 | P: PS3 + PM1 + PM2 + PM5 + PP3 + PP4 | NA |
TBK1 | NM_013254 p.Glu232Gln/c.694G > C | Missense | Novel | NA | D/D/N/D | 25.7 | NA | 0,0,0 | P: PS3 + PM1 + PM2 + PP3 + PP4 | NA |
TBK1 | NM_013254 p.Ser398Phe/c.1193C > T | Missense | Novel | NA | D/D/D/P | 20.3 | NA | 0,0,0 | LP: PS3 + PM2 + PP3 + PP4 | NA |
TBK1 | NM_013254 p.Thr78Ala/c.232A > G | Missense | Novel | NA | D/T/D/B | 22.5 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
TBK1 | NM_013254 p.Gln150Pro/c.449A > C | Missense | Novel | NA | D/D/N/D | 23.3 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
TBK1 | NM_013254 p.Trp259GlyfsTer52/c.775del | Frameshift | Novel | NA | D/-/-/- | - | NA | 0,0,0 | P: PVS1 + PS3 + PM2 + PP3 + PP4 | NA |
OPTN | NM_021980 p.Leu494Trp/c.1481T > G | Missense | Known | Rs777195053 | N/D/N/D | 28.6 | NA | 1/140202, 1/121406, 0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 24,908,169 |
OPTN | NM_021980 p.Glu516Gln/c.1546G > C | Missense | Known | Rs757107215 | D/T/D/P | 25.4 | P | 5/251460, 3/121358, 0 | P: PS1 + PM1 + PM2 + PP3 + PP4 | 26,503,823 |
OPTN | NM_021980 p.Arg144Gly/c.430A > G | Missense | Novel | Rs1431906155 | D/D/D/B | 22.9 | NA | 1/251474/-/- | P: PS3 + PM1 + PM2 + PP3 + PP4 | NA |
OPTN | NM_021980 p.Phe475Val/c.1423T > G | Missense | Novel | NA | D/D/D/D | 29.5 | NA | 0,0,0 | P: PS3 + PM1 + PM2 + PP3 + PP4 | NA |
OPTN | NM_021980 p.Thr282Pro/c.844A > C | Missense | Known | Rs773125318 | N/T/D/B | 7.139 | NA | 8/251478,5/121294,0 | LP: PM1 + PM2 + PP4 + PP5 | 21,613,650 |
OPTN | NM_021980 p. Ala136Val/c.407C > T | Missense | Known | Rs764364218 | N/T/D/B | 8.1 | VUS | 16/251442,4/121362,0 | LP: PM1 + PM2 + PP4 + PP5 | 26,503,823 |
GRN | NM_002087 p.Pro451Leu /c.1352C > T | Missense | Known | Rs752428000 | D/D/N/D | 28.1 | VUS | 1/140268, 1/120150, 0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 18,565,828 |
GRN | NM_002087 p.Val473fs/c.1414-14_1444del | Deletion/Frameshift | Novel | NA | D/-/-/- | - | NA | 0,0,0 | P: PVS1 + PS3 + PM2 + PP3 + PP4 | NA |
GRN | NM_002087 p.Thr487Ile/c.1460C > T | Missense | Known | Rs772784579 | D/D/D/P | 25.4 | VUS | 2/140306,0,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 29,530,724 |
GRN | NM_002087 p.Cys307GlufsTer3/c.914_915ins | Insertion/Frameshift | Novel | NA | D/-/-/- | - | NA | 0,0,0 | P: PVS1 + PS3 + PM2 + PP3 + PP4 | NA |
GRN | NM_002087 p.Asn119del/c.355_357del | Deletion | Known | Rs758168578 | D/-/-/- | - | VUS | 6/140088, 8/121346, 1/6404 | LP: PS4 + PM4 + PP4 + PP5 | 29,339,765 |
GRN | NM_002087 p.Arg101GlnfsTer13/c.302_315del | Deletion/Frameshift | Novel | NA | D/-/-/- | - | NA | 0,0,0 | P: PVS1 + PS3 + PM2 + PP3 + PP4 | NA |
ANXA11 | NM_001157 p.Asp40Gly/c.119A > G | Missense | Known | Rs1247392012 | D/T/D/P | 23.1 | P | 2/174858,0,0 | LP: PM1 + PM2 + PP2 + PP3 + PP4 + PP5 | 33,087,501 |
ANXA11 | NM_001157 p.Gln155*/c.463C > T | Nonsense | Novel | NA | D/-/-/- | - | NA | 0,0,0 | P: PVS1 + PM2 + PP3 + PP4 | NA |
ANXA11 | NM_001157 p.Pro36Arg/c.107C > G | Missense | Known | Rs199988035 | D/D/D/D | 23.5 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 36,458,208 |
CHMP2B | NM_014043 p.Arg186Gln/c.557G > A | Missense | Novel | Rs747423794 | D/T/D/B | 21.3 | NA | 0, 2/119998, 0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
CHMP2B | NM_014043 p.Arg205Trp/c.613C > T | Missense | Known | Rs373536428 | D/D/D/B | 23.1 | VUS | 12/250486,9/120064,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 29,411,640 |
CHMP2B | NM_014043 p.Lys6Asn/c.18G > T | Missense | Novel | NA | D/D/D/D | 23.3 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
CYLD | NM_015247 p.Gln443Lys/c.1327C > A | Missense | Known | Rs764952788 | D/T/D/P | 22.2 | NA | 4/249318,3/120728,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 34,868,212 |
CYLD | NM_015247 p.Thr157Ile/c.470C > T | Missense | Novel | NA | D/D/D/P | 21.9 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
SQSTM1 | NM_003900 p.Glu362Lys/c.1084G > A | Missense | Known | Rs535932454 | D/D/N/P | 23 | VUS | 1/140202, 4/121302, 1/5008 | LP: PS4 + PM1 + PP3 + PP4 | 31,859,009 |
SQSTM1 | NM_003900 p.Ser403Ala/c.1207T > G | Missense | Novel | NA | D/T/N/D | 26.3 | VUS | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
PRNP | NM_000311 p.Val180Ile/c.538G > A | Missense | Known | Rs74315408 | D/D/D/D | 22.5 | P/LP | 4/140106, 6/121398, 1/5008 | P: PS1 + PS3 + PM1 + PM2 + PP3 + PP4 + PP5 | 20,301,407 |
PRNP | NM_000311 2-OPRD | Deletion | Known | Rs193922906 | - | - | VUS | 0,0,0 | LP: PM1 + PM2 + PP4 + PP5 | 12,451,210; 11,468,331 |
VCP | NM_007126 p.Arg662Cys/c.1984C > T | Missense | Known | Rs765795425 | D/D/D/D | 31 | VUS | 1/249512,1/120766,0 | LP: PM1 + PM2 + PP3 + PP4 + PP5 | 22,572,540 |
TARDBP | NM_007375 p.Ile383Val/c.1147A > G | Missense | Known | Rs80356740 | D/T/N/B | 17.19 | P | 4/230726, 1/115618, 0 | LP: PS1 + PM1 + PP2 + PP4 | 18,802,454; 26,581,115; 30,773,994 |
UBQLN2 | NM_013444 p.Pro509His/c.1526C > A | Missense | Novel | Rs868418213 | N/D/N/P | 23.4 | NA | 0,0,0 | LP: PM2 + PM5 + PP2 + PP3 + PP4 | NA |
CCNF | NM_001761 p.Ser160Asn/c.479G > A | Missense | Novel | NA | D/T/D/D | 19.6 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
CHCHD10 | NM_213720 p.Ala8Thr/c.22G > A | Missense | Novel | NA | N/T/D/B | 11.57 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
SIGMAR1 | NM_005866 p.Ser117Leu/c.350C > T | Missense | Novel | NA | D/D/D/D | 33 | NA | 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 | NA |
CHCHD2 | NM_001320327 p.Pro53fs/c.153_156dupGCAG | Frameshift | Novel | NA | D/-/-/- | - | NA | 0,0,0 | P: PVS1 + PM2 + PP3 + PP4 | NA |
FUS | NM_004960 p.Ser235Gly/c.703A > G NM_004960 p.Ser236Gly/c.706A > G | Missense Missense | Novel Novel | NA NA | N/T/D/B N/T/D/B | 17.33 17.23 | NA NA | 0,0,0 0,0,0 | LP: PM1 + PM2 + PP3 + PP4 LP: PM1 + PM2 + PP3 + PP4 | NA NA |
TMEM106B | NM_001134232 p.Leu144Val/c.430T > G | Missense | Novel | NA | D/D/D/P | 24.7 | NA | 0,0,0 | LP: PM1 + PM2 + PP2 + PP3 + PP4 | NA |