Table 3:
Intersection between pathogenic CNVs and recurrently mutated genes.
| denovo-db v.1.5
Counts |
Union CH Model and denovolyzeR | Genomic Disorders | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LGD de novo Variants | Missense de novo Variants | MIS30 de novo Variants | |||||||||||||
| Gene Symbol* | All (n=10,927) | ASD (n=5,624) | ID/DD (n=5,303) | All (n=10,927) | ASD (n=5,624) | ID/DD (n=5,303) | All (n=10,927) | ASD (n=5,624) | ID/DD (n=5,303) | Significance (FDR ≤ 5%, count > 1) | Deletion Syndrome | Duplication Syndrome | CNV Significance Type18 | Decipher† Classification | |
| Significant in Morbidity Map18 (37 Disorders) | MAPK3 | 0 | 0 | 0 | 3 | 2 | 1 | 1 | 1 | 0 | MIS | 16p11.2-deletion | 16p11.2-duplication | DEL AND DUP | |
| KANSL1 | 8 | 0 | 8 | 1 | 1 | 0 | 0 | 0 | 0 | LGD | 17q21.31-deletion | 17q21.31-duplication | DEL | Category 1 | |
| KIF1A | 0 | 0 | 0 | 11 | 1 | 10 | 9 | 0 | 9 | MIS | 2q37-deletion | None | DEL | Category 1 | |
| EHMT1 | 9 | 0 | 9 | 3 | 0 | 3 | 2 | 0 | 2 | LGD | 9q34-deletion | 9q34-duplication | DEL AND DUP | Category 1 | |
| SHANK3 | 10 | 6 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | LGD | Phelan-McDermid-syndrome-deletion | None | DEL AND DUP | Category 1 | |
| PHF21A | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | LGD | Potocki-Shaffer-syndrome | None | DEL | Category 1 | |
| GABRB3 | 1 | 1 | 0 | 6 | 2 | 4 | 0 | 0 | 0 | MIS | Prader-Willi/Angelman | PWS-duplication | DEL AND DUP | Category 1 | |
| RAI1 | 3 | 1 | 2 | 3 | 2 | 1 | 0 | 0 | 0 | LGD | Smith-Magenis-syndrome-deletion | Potocki-Lupski-syndrome-duplication | DEL AND DUP | Category 1 | |
| NSD1 | 8 | 1 | 7 | 5 | 2 | 3 | 1 | 0 | 1 | LGD | Sotos-syndrome-deletion | None | DEL | Category 1 | |
| WHSC1 | 4 | 1 | 3 | 2 | 1 | 1 | 1 | 0 | 1 | LGD | Wolf-Hirschhorn-deletion | None | DEL AND DUP | Category 1 | |
| 21 Additional Genomic Disorders | SIN3A | 3 | 0 | 3 | 3 | 2 | 1 | 1 | 0 | 1 | LGD | 15q24 deletion (A to E Inclusive) | None | Other SD Pairs | |
| CLTC | 4 | 0 | 4 | 2 | 0 | 2 | 1 | 0 | 1 | LGD | 17q23 deletion | None | |||
| PPM1D | 8 | 1 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | LGD | 17q23.1q23.2 deletion | None | |||
| BCL11A | 6 | 2 | 4 | 3 | 0 | 3 | 0 | 0 | 0 | LGD | 2p15-16.1 microdeletion syndrome | None | |||
| PAPOLG | 0 | 0 | 0 | 3 | 3 | 0 | 3 | 3 | 0 | MIS30 | 2p15-16.1 microdeletion syndrome | None | |||
| POU3F3 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 0 | 2 | LGD | 2q11.2q13 deletion | None | |||
| RFX8 | 0 | 0 | 0 | 3 | 2 | 1 | 0 | 0 | 0 | MIS | 2q11.2q13 deletion | None | |||
| HECW2 | 1 | 0 | 1 | 9 | 2 | 7 | 7 | 2 | 5 | MIS30 & MIS | 2q33.1 | None | Category 1 | ||
| SATB2‡ | 9 | 0 | 9 | 6 | 0 | 6 | 5 | 0 | 5 | LGD & MIS30 & MIS | 2q33.1 | None | Category 1 | ||
| ABI2 | 0 | 0 | 0 | 3 | 2 | 1 | 1 | 1 | 0 | MIS | 2q33.1 | None | Category 1 | ||
| SF3B1 | 0 | 0 | 0 | 5 | 3 | 2 | 1 | 0 | 1 | MIS | 2q33.1 | None | Category 1 | ||
| CAPN15 | 0 | 0 | 0 | 3 | 0 | 3 | 1 | 0 | 1 | MIS | ATR-16 | None | Category 1 | ||
| SMC1A | 8 | 0 | 8 | 2 | 0 | 2 | 1 | 0 | 1 | LGD | None | Xp11.22-linked ID | |||
| HUWE1 | 0 | 0 | 0 | 9 | 0 | 9 | 3 | 0 | 3 | MIS | None | Xp11.22-linked ID | |||
| WDR45 | 8 | 0 | 8 | 2 | 1 | 1 | 0 | 0 | 0 | LGD | None | Xp11.22-p11.23 microduplication | |||
| MECP2 | 11 | 4 | 7 | 7 | 0 | 7 | 4 | 0 | 4 | LGD & MIS30 & MIS | None | Xq28 (MECP2) duplication | |||
| CREBBP | 3 | 0 | 3 | 13 | 3 | 10 | 1 | 1 | 0 | LGD & MIS | Rubinstein-Taybi syndrome | None | Category 1 | ||
| SUV420H1 | 7 | 4 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | LGD | SHANK2 FGFs deletion | None | |||
| YWHAG | 0 | 0 | 0 | 3 | 1 | 2 | 1 | 0 | 1 | MIS | Wms-distal deletion | Wms-distal duplication | |||
| AUTS2 | 4 | 0 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | LGD | Wms-prox deletion | Wms-prox duplication | |||
| 14 Significant Regions18 | SATB2‡ | 9 | 0 | 9 | 6 | 0 | 6 | 5 | 0 | 5 | LGD & MIS30 & MIS | 2q33.1 (SATB2) deletion | |||
| MEF2C | 4 | 0 | 4 | 5 | 1 | 4 | 0 | 0 | 0 | LGD & MIS | 5q14 (MEF2C) deletion | ||||
| CHD4 | 1 | 0 | 1 | 8 | 1 | 7 | 2 | 0 | 2 | MIS | 12p13 (SCNN1A to PIANP) | ||||
| WDFY4 | 0 | 0 | 0 | 5 | 4 | 1 | 1 | 0 | 1 | MIS | 1q11.23 duplication | ||||
DNM counts and significance categories from n = 10,927 independent samples are shown for genes from the union significance set (n = 253 genes denovolyzeR or CH model FDR < 5%) that intersect a previously established genomic disorder region. Gene symbols with underlines represent confirmation of known CNV associations. SD: segmental duplication
†
DECIPHER syndrome classification system; see URLs.
‡
SATB2 is significant both by focal deletions and as part of the 2q33.1 region.