Table 1. Prevalence of six reported pathogenic SNCA mutations and LRRK2 Gly2019Ser in large population databases and pathogenicity algorithm scores.
Twenty-two individuals in gnomAD (3 Africans and 19 Europeans, n=138,587) and seven individuals in HRC (all Europeans, n=32,488) were heterozygous for SNCA His50Gln (Lek et al., 2016; McCarthy et al., 2016). The LRRK2 Gly2019Ser mutation was found in 136 individuals in gnomAD (3 African, 8 Latino, 118 European [including Ashkenazi Jewish] and 7 other) and 13 individuals in the HRC (all Europeans). gnomAD = Genome Aggregation Database, HRC = Haplotype Reference Consortium, D = damaging, T = tolerant, B = benign.
| Gene: amino acid change | rs number | chr:bp (hg19) | gnomAD (frequency) | HRC (frequency) | SIFT (score) | Polyphen2 (score) | CADD phred | DANN score | GERP++ RS |
|---|---|---|---|---|---|---|---|---|---|
| SNCA: Ala30Pro (Kruger et al., 1998) | rs104893878 | 4:90756731 | 0 | 0 | D (0.001) | D (0.996) | 32 | 0.998 | 4.28 |
| SNCA: Glu46Lys (Zarranz et al., 2004) | rs104893875 | 4:90749321 | 0 | 0 | D (0.006) | B (0.426) | 26.4 | 0.998 | 3.55 |
| SCNA: His50Gln (Appel-Cresswell et al., 2013; Proukakis et al., 2013) | rs201106962 | 4:90749307 | 22 (0.0079%) | 7 (0.011%) | T (1) | B (0.012) | 0.007 | 0.425 | −2.19 |
| SNCA: Gly51Asp (Kiely et al., 2013; Lesage et al., 2013) | rs431905511 | 4:90749305 | 0 | 0 | D (0.004) | D (0.999) | 23.9 | 0.996 | 3.55 |
| SNCA: Ala53Glu (Pasanen et al., 2014) | n/a | 4:90749299 | 0 | 0 | D (0.007) | B (0.015) | 15.99 | 0.952 | 4.39 |
| SNCA: Ala53Thr (Polymeropoulos et al., 1997) | rs104893877 | 4:90749300 | 0 | 0 | T (1) | B (0) | 10.48 | 0.203 | 3.12 |
| LRRK2: Gly2019Ser (Gilks et al., 2005) | rs34637584 | 12:40734202 | 136 (0.049%) | 13 (0.020%) | D (0) | D (1) | 35 | 0.998 | 5.69 |