Table 5.
Variants present in the enriched genes (gene-based aggregation analysis).
| Gene | codon | Reference | Associated disease (HGMD) | ACMG | AF_GNOMEX_NFE | Cohort MAF | % pts | % HC | N pts (n = 22) | N HC (n = 73) |
|---|---|---|---|---|---|---|---|---|---|---|
| CD33 | S305P | NM_001772.3:c.913 T > C | nr | benign | 2.15E-02 | 2.60% | 8.70% | 0.70% | 4 | 1 |
| CD33 | G156fs | NM_001772.3:c.466_469delGGCC | AD risk | benign | 2.43E-02 | 2.60% | 2.20% | 2.70% | 1 | 4 |
| CD33 | F243L | NM_001772.3:c.727 T > C | nr | benign | 3.58E-04 | 0.50% | 2.20% | 0.00% | 1 | 0 |
| CD33 | V267I | NM_001772.3: c.799G > A | nr | benign | 4.39E-04 | 0.50% | 2.20% | 0.00% | 1 | 0 |
| PSEN1 | E318G | NM_000021.3:c.953A > G | AD risk | benign | 1.86E-02 | 1.60% | 4.30% | 0.70% | 2 | 1 |
| PSEN1 | M93V | NM_000021.3:c.277A > G | nr | Likely pathogenic | 8.95E-06 | 0.50% | 2.20% | 0.00% | 1 | 0 |
| PSEN1 | D333V | NM_000021.3:c.998A > T | nr | Likely pathogenic* | 0 | 0.50% | 0.00% | 0.70% | 0 | 1 |
| OPTN | M98K | NM_001008211.1:c.293 T > A | glaucoma risk | Likely benign | 2.80E-02 | 3.10% | 6.50% | 2.10% | 3 | 3 |
| OPTN | Q314L | NM_001008211.1:c.941A > T | ALS | VUS-LP | 2.78E-04 | 0.50% | 2.20% | 0.00% | 1 | 0 |
| ABCA1 | Q2196H | NM_005502.3:c.6588G > C | HDL deficiency | VUS-LP | 2.25E-04 | 0.50% | 2.20% | 0.00% | 1 | 0 |
| ABCA1 | R909Q | NM_005502.3:c.2726G > A | nr | VUS | 2.69E-05 | 0.50% | 0.00% | 0.70% | 0 | 1 |
| ABCA1 | T774P | NM_005502.3:c.2320A > C | Increased cholesterol | Likely benign | 3.15E-03 | 0.50% | 0.00% | 0.70% | 0 | 1 |
| ABCA1 | M674L | NM_005502.3:c.2020A > C | nr | VUS | 0 | 0.50% | 2.20% | 0.00% | 1 | 0 |
| ABCA1 | V285M | NM_005502.3:c.853G > A | nr | VUS | 1.79E-05 | 0.50% | 2.20% | 0.00% | 1 | 0 |
| ABCA1 | . | NM_005502.3:c.814-7A > G | nr | VUS | . | 0.50% | 2.20% | 0.00% | 1 | 0 |
| ABCA1 | K776N | NM_005502.3:c.2328G > C | Risk ischemic heart disease | Benign | 3.38E-03 | 1.00% | 0.00% | 1.40% | 0 | 2 |
| ABCA1 | E1172D | NM_005502.3:c.3516G > C | Coronary heart disease | Benign | 2.90E-02 | 4.20% | 0.00% | 5.50% | 0 | 7 |
| ABCA1 | V771M | NM_005502.3:c.2311G > A | Altered cholesterol levels | Benign | 3.32E-02 | 4.70% | 0.00% | 6.20% | 0 | 8 |
HGMD = Human Gene Mutation Database; nr = not reported; ALS = Amyotrophic lateral sclerosis; AD = Alzheimer’s disease; HDL = high-density lipoprotein; ACMG = American College of Medical Genetics; VUS = variant of unknown significance; VUS-LP = VUS near likely pathogenic; AF_GNOMEX_NFE = Allele frequency from Genome Aggregation Database - Exome - Non Finnish Europeans. MAF = Minor allele frequency;
*
for cardiovascular disease; N = number; pts = patients; HC = Healthy controls.