Table 3.
Variant details and respective classification scores for 16p11.2del CNV and CHD8 test cases
| Sample ID | Sex | Age (years) | 16p11.2del coordinates (size in kb) | Diagnostic classification for 16p11.2 typical deletion (pathogenic, benign, variant of unknown significance [VUS]) | Inheritance | ASD status | 16p11.2del score |
|---|---|---|---|---|---|---|---|
| 348 | M | 0.25 | 29,590,493–30,190,593 (600) | Pathogenic | Unknown | Unknown | 0.11505 |
| 228 | M | 0.4 | 29,590,493–30,190,593 (600) | Pathogenic | Unknown | Unknown | 0.12668 |
| 875 | F | 4 | 29,656,657–30,190,593 (534) | Pathogenic | Unknown | Unknown | 0.03073 |
| 172 | F | 6 | 29,590,493–30,190,593 (600) | Pathogenic | Unknown | Unknown | 0.04668 |
| 292 | M | 0.25 | 29,500,252–30,098,094 (598) | Pathogenic | Unknown | Unknown | 0.13978 |
| 2-0088-003 | F | 12 | 29,652,799–30,199,507 (547) | Pathogenic (MOSAIC) | De novo | ASD | -0.00441 |
| 3-0406-000 | M | 1.2 | 29,581,764–30,199,579 (618) | Pathogenic | Unknown | ASD | 0.07735 |
| 6-0196-03 | M | Unknown | 29,500,084–30,098,210 (598) | Pathogenic | Unknown | ASD | 0.04815 |
| 1-0616-003 | M | 7.5 | 28,751,255–28,952,351 (201) | Not determined* | Maternal | ASD | − 0.11936 |
| Sample ID | Sex | Age (years) | CHD8 variant nucleotide change; amino acid change (Exon #) | Diagnostic classification (pathogenic, benign, variant of unknown significance [VUS]) | Inheritance | ASD status | CHD8+/− score |
| 14406.p1 | M | 13 | c.7493_7495del; p.His2498del (37) | VUS | De novo | ASD | − 0.03482 |
| 1-0494-003 | M | 4.75 | c.2219A>G; p.Asn740Ser (9) | Benign | Paternal | ASD | − 0.04451 |
| 2-1228-003 | F | 4.5 | c.6841C>G; p.Pro2281Ala (34) | Benign | Paternal | ASD | − 0.04178 |
| 1-0277-003 | M | Unknown | c.6565G>A; p.Gly2189Arg (33) | Benign | Maternal | ASD | − 0.03065 |
| 1-0507-003 | F | 14 | c.3940G>A; p.Ala1314Thr (19) | Benign | Maternal | ASD | − 0.05507 |
| 7-0167-003 | M | 4 | c.7499A>C; p.His2500Pro (37) | Benign | Unknown | ASD | − 0.05984 |
| 1-0559-003 | M | 7.7 | c.6148dupA; p.Thr2050fs (31) | Pathogenic | De novo | ASD | 0.0437 |
| CHD8-V1 | M | 10 | c.4215G>T; Synonymous (21) | VUS | Paternal | ASD | − 0.04478 |
| CHD8-V2 (father of CHD8-V1) | M | 40 | c.4215G>T; Synonymous (21) | VUS | Not applicable | Unaffected | − 0.04332 |
| CHD8-V3** | M | 6.5 | c.6649C>T, p.Arg2217* (33) | Pathogenic | Paternal | ASD | 0.04616 |
| CHD8-V4 (sibling of CHD8-V3)** | M | 14 | c.6649C>T, p.Arg2217* (33) | Pathogenic | Paternal | ASD | 0.03631 |
| DW0013** | M | 13.5 | c.6947delC, p.Pro2316Leufs*39 (35) | Likely pathogenic | Unknown | ASD | 0.05183 |
| EX0070-W** | M | 6.75 | c.4327C>T, p.Arg1443Cys (21) | VUS | Paternal | ASD | − 0.04131 |
*Deletion encompassing SH2B1 gene, not overlapping 16p11.2del typical deletion region
**Test case data are from EPIC array, classified using 93 probes overlapping 450K and EPIC arrays from CHD8+/− signature