Table 2.
Overview of variants in the KIF1A gene identified in ALS patients.
| ID | Position (hg19) | Refseq ID | cDNA change | Protein change | dbSNP | Minor allele frequencies | Functional predictions | ACMG | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| gnomAD_genome_ALL | gnomAD_exome_ALL | SIFT | Polyphen2 | MutationTaster | MetaSVM | MetaLR | ClinPred | M_CAP | CADD | Pathogenic (total) | Evidence | Classification | ||||||
| P1 | chr2:241710533 | NM_001330290 | c.1271C>T | p.Pro424Leu | rs1254343314 | – | – | – | – | – | – | – | – | – | – | – | PM2 | VUS |
| P2 | chr2:241696840 | NM_001244008 | c.2753_2754insGGA | p.Asp918delinsGluAsp | rs758125020 | 1.68E-02 | 1.74E-02 | – | – | – | – | – | – | – | – | – | PM2, PM4 | VUS |
| P3 | chr2:241689888 | NM_001244008 | c.2935G>A | p.Glu979Lys | rs764324827 | – | 4.00E-06 | T | P | D | T | D | D | D | 35 | 6 (8) | PM2, BP4 | VUS |
| P4 | chr2:241685282 | NM_001244008 | c.3247G>A | p.Ala1083Thr | rs201793635 | 4.00E-04 | 3E-06 | T | B | P | T | T | T | D | 5.97 | 1 (8) | BP4 | VUS |
| P5 | chr2:241685282 | NM_001244008 | c.3247G>A | p.Ala1083Thr | rs201793635 | 4.00E-04 | 3.00E-04 | T | B | P | T | T | T | D | 5.97 | 1 (8) | BP4 | VUS |
| P6 | chr2:241683410 | NM_001244008 | c.3533 T>C | p.Phe1178Ser | - | – | – | D | D | D | – | – | – | – | 25.6 | 3 (3) | PM2, PM1, PP3 | VUS |
| P7 | chr2:241680755 | NM_001244008 | c.3680C>T | p.Pro1227Leu | rs374244985 | 2.00E-04 | 2.00E-04 | T | B | D | T | T | T | D | 21.2 | 3 (8) | PM1, BP4 | VUS |
| P8 | chr2:241679768 | NM_001244008 | c.3763G>A | p.Val1255Met | rs752703226 | – | 1.20E-05 | D | D | D | T | T | D | D | 24.2 | 6 (8) | PM2, PM1, PP2, PP3 | LP |
| P9 | chr2:241661285 | NM_001244008 | c.4682C>T | p.Thr1561Met | rs769101887 | – | 4.00E-06 | T | B | D | T | T | T | D | 19.77 | 3 (8) | PM2, PM1, BP4 | VUS |
| P10 | chr2:241660421 | NM_001244008 | c.4778C>T | p.Pro1593Leu | rs200902828 | 3.00E-04 | 5.00E-04 | D | B | D | T | T | T | D | 23.6 | 4 (8) | PM2, PM1, PP2, PP3 | LP |
| P11 | chr2:241659285 | NM_001244008 | c.4927G>A | p.Asp1643Asn | rs200141437 | 1.00E-04 | 3.00E-04 | T | B | D | T | T | T | T | 18.6 | 2 (8) | PM2, PS4, PM1, PP2, BP4 | LP |
| P12 | chr2:241659257 | NM_001244008 | c.4955G>A | p.Arg1652Gln | rs376658420 | 9.70E-05 | 2.00E-04 | T | B | P | T | T | T’ | T | 6.526 | 0 (8) | PM2, PM1, BP4 | VUS |
| P13 | chr2:241658506 | NM_001244008 | c.5131G>A | p.Asp1711Asn | rs199574770 | 3.20E-05 | 5.70E-05 | D | D | D | T | T | T | D | 34 | 5 (8) | PM1, PP3 | VUS |
| P14 | chr2:241658487 | NM_001244008 | c.5150G>T | p.Arg1717Leu | rs760970824 | 5.00E-05 | 2.40E-05 | D | D | D | T | T | D | D | 35 | 6 (8) | PM2, PM1, PP2, PP3 | LP |
ALS, amyotrophic lateral sclerosis; SNP, Single-nucleotide polymorphism; ACMG, American College of Medical Genetics and Genomics; VUS, uncertain significance; LP, likely pathogenic; HGMD, Human Gene Mutation Database; SIFT, sorting intolerant from tolerant; PolyPhen2, polymorphism phenotyping version 2; SVM, support vector machine; CADD, combined annotation dependent depletion; M_CAP, Mendelian clinically applicable pathogenicity; SIFT (D: Damaging; T: Tolerable); Polyphen2 (D: Probably_Damaging; P: Possibly_Damaging; B:Benign); Mutation Taster (D: Disease_causing; P: Polymorphism); MetaSVM (T: Tolerable); MetaLR (D: Damaging; T: Tolerable); ClinPred (D: Deleterious; T: Tolerable); M_CAP (D: Damaging; T: Tolerable); CADD: (D: Damaging; T: Tolerable).