Table 2.
Copy number variations (CNVs) identified in the ALS proband by NeuroArray aCGH.
| Chr | Start | Stop | Probes | Log2 Ratio (Test/Control) | p-Value | Gene | Common CNV (DGV Frequency) | qPCR Validation | Clinical Interpretation | Detected in SCA1-MN Family Members (Patient Code) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 98,164,881.00 | 98,187,177.00 | 6 | −0.63967 | 1.54 × 10−10 | DPYD | Yes (0.005–0.04%) | Likely pathogenic | No | |
| 2 | 64,146,992 | 64,211,176.00 | 25 | −0.3406 | 5.01 × 10−13 | VPS54 | Yes (0.003%) | X | Likely pathogenic | Yes (IV-18 *, IV-13, IV-15) |
| 2 | 166,852,501 | 166,870,328.00 | 14 | −0.5323 | 4.49 × 10−14 | SCN1A | Not | Likely pathogenic | No | |
| 2 | 166,911,120 | 166,913,035.00 | 5 | −0.67504 | 5.51 × 10−11 | SCN1A | Yes (0.1%) | Likely pathogenic | No | |
| 2 | 167,328,904 | 167,334,011.00 | 6 | −0.75482 | 4.24 × 10−11 | SCN7A | Yes (0.005–1%) | X | Likely pathogenic | No |
| 2 | 179,536,740 | 179,540,750.00 | 9 | −0.57381 | 1.35 × 10−10 | TTN | Yes (0.4%) | Likely pathogenic | No | |
| 3 | 87,299,007 | 89,814,870.00 | 10 | −0.45231 | 1.51 × 10−10 | CHMP2B, EPHA3 | Yes (0.003–1%) | X | Uncertain clinical significance | No |
| 3 | 93,772,085 | 113,652,487.00 | 20 | −0.28537 | 4.68 × 10−11 | ARL13B | Yes (0.006–0.03%) | Uncertain clinical significance | No | |
| 6 | 161,026,135 | 161,067,305.00 | 17 | 0.477799 | 2.80 × 10−21 | LPA | Yes (>70%) | Likely benign | No | |
| 7 | 17,362,101 | 17,375,411.00 | 12 | −0.64847 | 3.43 × 10−22 | AHR | Yes (0.0034–0.04%) | Likely pathogenic | Yes (IV-13) | |
| 8 | 30,947,985 | 30,999,316.00 | 23 | −0.30766 | 1.60 × 10−11 | WRN | Not | Likely pathogenic | No | |
| 9 | 27,558,554 | 27,573,862.00 | 13 | −0.39928 | 2.08 × 10−11 | C9orf72 | Not | X | Likely pathogenic | No |
| 10 | 70,892,631 | 70,931,418.00 | 15 | −0.36405 | 4.32 × 10−10 | VPS26A | Yes (>10%) | Likely benign | No | |
| 17 | 44,301,037 | 44,771,900.00 | 16 | −0.61264 | 4.50 × 10−29 | NSF | Yes | X | Likely benign | Yes (IV-18, IV-13, IV-15) |
| 21 | 38,791,571 | 38,865,493.00 | 15 | −0.35809 | 8.53 × 10−11 | DYRK1A | Yes (0.003–5%) | Uncertain clinical significance | Yes (IV-13) | |
| X | 108,902,635 | 108,906,573.00 | 6 | −0.73236 | 5.03 × 10−10 | ACSL4 | Yes (2%) | Likely benign | No |
Chromosome coordinates are given according to hg19 assembly (UCSC genome browser https://genome.ucsc.edu/). ALS genes inside CNVs are depicted in bold. Log2 ratio (test/ctrl) = duplications (red), deletions (blue). Database of Genomic Variants (DGV) frequency indicates the population frequency of respective CNV in the Database of Genomic Variants (DGV, http://dgv.tcag.ca/dgv/app/home). Clinical interpretation was manually assessed and classified into different categories, according to the American College of Medical Genetics and Genomics (ACMG) guidelines for CNVs. Of note, some of the alterations reported here were previously described to validate the NeuroArray v.1 platform as a genomic profiling assay for ALS [13]. * Sample IV-18 reported a duplication in the same genomic region.