TABLE 4.
Rare variants in other dementia causative genes identified in this study.
| Gene | ID patient | FH score |
Nucleotide change | Protein change | Pathogenicity ClinVar/HGMD | Frequency GnomAD (EU)1 | P-value2 |
| CCNF | AD#020 | 0 | c.353T > C | p.Val118Ala | NR/NR/prediction – Likely pathogenic | 1/111550 | 0.02 |
| AD#079 | 1.5 | c.656T > C | p.Leu219Pro | NR/NR/prediction – Likely pathogenic | 5/111832 | 0.03 | |
| CHCHD10 | AD#068 | 0 | c.354C > A | p.Asp118Glu | Uncertain significance/NR | NR | NA |
| CSF1R | AD#081 | 0 | c.1400C > T | p.Thr467Met | NR/NR/prediction – Likely benign | 5/113734 | 0.03 |
| AD#057 | 3.5 | c.1477A > G | p.Ser493Gly | NR/NR/prediction – Likely benign | NR | NA | |
| AD#044 | 0 | c.2850C > A | p.His950Gln | NR/NR/prediction – Likely benign | 2/113066 | 0.02 | |
| c.2851C > A | p.Leu951Met | NR/NR/prediction – Likely benign | 2/113102 | 0.02 | |||
| DCTN1 | AD#102 | 3.5 | c.586A > G | p.Ile196Val | Conflicting interpretations of pathogenicity. Uncertain significance (2); Benign (6)/abnormal cellular organization. |
649/105456 | 1 |
| AD#030 | 0 | c.1361T > C | p.Val454Ala | NR/NR/prediction – Likely pathogenic | NR | NA | |
| AD#100 | 3 | c.1480G > A | p.Ala494Thr | Uncertain significance/amyotrophic lateral sclerosis, phenotype modifiers? | 4/128890 | 0.03 | |
| AD#067 | 0 | c.1555A > G | p.Lys519Glu | NR/NR prediction: Likely pathogenic | NR | NA | |
| AD#070 | 1 | c.2278A > G | p.Met760Val | Conflicting interpretation of pathogenicity Uncertain significance (2) Benign (2) Likely benign (1)/NR | 10/129140 | 0.03 | |
| AD#078 | 0 | c.2989C > T | p.Arg997Trp | Uncertain significance/amyotrophic lateral sclerosis. | 1/113370 | 0.02 | |
| FIG4 | AD#080 | 0 | c.2200G > A | p.Glu734Lys | Uncertain significance/NR | 15/113494 | 0.04 |
| AD#097 | 0 | c.2467C > T | p.Gln823Ter* | Pathogenic/NR | 7/129138 | 0.03 | |
| FUS | AD#039 | 0 | c.430_447del | p.Gly144_Tyr149del | Conflicting interpretations of pathogenicity. Pathogenic (1); likely pathogenic (1); uncertain significance (1)/NR |
10/113750 | 0.03 |
| AD#033 | 1.5 | c.681_686del | p.Gly230_Gly231del | Conflicting interpretations of pathogenicity benign (1) uncertain significance (1)/NR | 56/117710 | ||
| AD#049 | 3.5 | 0.11 | |||||
| MAPT | AD#039 | 0 | c.121G > A | p.Ala41Thr | Uncertain significance/Alzheimer disease? | 6/128512 | 0.03 |
| AD#017 | 3.5 | c.454G > A | p.Ala152Thr | Conflicting interpretation of pathogenicity uncertain significance (2) benign (1) likely benign (2)/neurodegeneration | 297/129002 | 0.39 | |
| NOTCH3 | AD#085 | 0 | c.1505C > T | p.Ser502Phe | Uncertain significance/NR | 9/75540 | 0.04 |
| AD#071 | 3 | c.3315C > T | p.Gly1105= | NR/NR/prediction: likely benign | 1/113330 | 0.02 | |
| AD#099 | 0 | c.3535A > G | p.Asn1179Asp | NR/NR/prediction: likely pathogenic | NR | NA | |
| AD#074 | 3.5 | c.4461C > T | p.Gly1487= | NR/NR/prediction: likely benign | NR | NA | |
| AD#093 | 3.5 | c.5816-6C > T | NR/NR prediction: likely benign | 6/113474 | 0.03 | ||
| OPTN | AD#010 | 3.5 | c.448C > T | p.Leu150= | NR/NR prediction: likely benign | 7/129170 | 0.03 |
| AD#091 | 3.5 | c.941A > T | p.Gln314Leu | Conflicting interpretations of pathogenicity pathogenic (1) uncertain significance (1)/amyotrophic lateral sclerosis | 38/129076 | 0.08 | |
| AD#069 | 0 | c.1401 + 4A > G | Uncertain significance/amyotrophic lateral sclerosis | 17/129180 | 0.05 | ||
| AD#053 | 0 | c.1643G > A | p.Arg548Gln | Uncertain significance/NR | 9/129122 | 0.03 | |
| SQSTM1 | AD#066 | 0 | c.315C > T | p.Cys105= | NR/NR prediction: likely benign | NR | NA |
| AD#092 | 3.5 | c.960G > A | p.Gly320= | NR/NR prediction: likely benign | 1/81718 | 0.02 | |
| AD#032 | 3.5 | c.1175C > T | p.Pro392Leu | Conflicting interpretations of pathogenicity pathogenic (4) likely pathogenic (1) uncertain significance (2) benign (1)/paget disease of bone | 173/128718 | 0.27 | |
| TYROBP | AD#077 | 0 | c.140T > C | p.Val47Ala | Uncertain significance – Alzheimer disease, early onset? | 14/128556 | 0.04 |
| UBQLN2 | AD#095 | 0 | c.1461C > A | p.Thr487= | Conflicting interpretations of pathogenicity uncertain significance (1); benign (5); likely benign (1)/NR | 787/87391 | 1 |
Only variants not previously defined as benign/likely benign in ClinVar and MAF < 0.01 referred to the European (non-Finnish) population reported on GnomAD v2.1.1. were selected and reported. Prediction of variant pathogenicity were reported in the Supplementary Tables 2–4. AD, Alzheimer disease, FH, family history, NR. Not reported RE, reported. 1Population allele frequencies referred to the European (non-Finnish) population reported on GnomAD v2.1.1. 2P-value Fisher’s exact test. *Variant homozygous.