Appendix Table 1.
CYP2C copy number variants (CNVs) identified in the Database of Genomic Variants (DGV), ClinGen, and DECIPHER.
| CNV ID | Genes | CNV type | Region size | Frequency | Study population | Ref. |
|---|---|---|---|---|---|---|
| DGV | ||||||
| esv3624253 | CYP2C18 | Deletion | 118,150 | 1/2504 | Healthy | (Genomes Project et al., 2015) |
| esv2672446 | CYP2C18 | Deletion | 118,136 | 1/1092 | Healthy | (Genomes Project et al., 2012) |
| esv3624254 | CYP2C18 | Deletion | 79,667 | 3/2504 | Healthy | (Genomes Project et al., 2015) |
| dgv955n100 | CYP2C18 | Deletion | 111,509 | 6/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| nsv551954 | CYP2C18 | Deletion | 115,921 | 2/15767 | Intellectual disability and/or developmental delay | (Cooper et al., 2011) |
| dgv956n100 | CYP2C18 | Deletion | 69,696 | 2/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| esv2657299 | CYP2C18 | Deletion | 8,618 | 1/1092 | Healthy | (Genomes Project et al., 2012) |
| nsv522538 | CYP2C18, CYP2C19 | Deletion | 142,135 | 1/2026 | Healthy | (Shaikh et al., 2009) |
| dgv1355n54 | CYP2C18, CYP2C19 | Deletion | 246,123 | 3/15767 | Intellectual disability and/or developmental delay | (Cooper et al., 2011) |
| esv2674280 | CYP2C18, CYP2C19 | Deletion | 155,809 | 1/1092 | Healthy | (Genomes Project et al., 2012) |
| nsv1046308 | CYP2C18, CYP2C19 | Deletion | 191,713 | 1/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| dgv1355n54 | CYP2C18, CYP2C19 | Deletion | 246,123 | 3/15767 | Intellectual disability and/or developmental delay | (Cooper et al., 2011) |
| dgv957n100 | CYP2C18, CYP2C19 | Deletion | 70,440 | 5/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| esv3624256 | CYP2C18, CYP2C19 | Deletion | 44,223 | 2/2504 | Healthy | (Genomes Project et al., 2015) |
| esv2761617 | CYP2C18, CYP2C19 | Deletion | 53,597 | 1/1109 | Healthy | (Vogler et al., 2010) |
| esv3624258 | CYP2C18, CYP2C19 | Duplication | 80,151 | 1/2504 | Healthy | (Genomes Project et al., 2015) |
| dgv160e214 | CYP2C18, CYP2C19 | Deletion | 80,151 | 1/2504 | Healthy | (Genomes Project et al., 2015) |
| dgv1356n54 | CYP2C18, CYP2C19 | Deletion | 61,544 | 6/15767 | Intellectual disability and/or developmental delay | (Cooper et al., 2011) |
| esv3891886 | CYP2C18, CYP2C19, CYP2C9 | Deletion | 271,380 | 1/3017 | Infectious diseases, Thyrotoxic Hypokalemic Periodic Paralysis (THPP) and Hb E/b-thalassemia | (Suktitipat et al., 2014) |
| nsv1035409 | CYP2C18, CYP2C19, CYP2C9, CYP2C8 | Deletion | 336,881 | 1/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| nsv551962 | CYP2C19 | Deletion | 54,075 | 1/15767 | Intellectual disability and/or developmental delay | (Cooper et al., 2011) |
| esv2659638 | CYP2C19 | Deletion | 61,848 | 1/1092 | Healthy | (Genomes Project et al., 2012) |
| esv3624260 | CYP2C19 | Deletion | 39,678 | 2/2504 | Healthy | (Genomes Project et al., 2015) |
| nsv516555 | CYP2C19 | Deletion | 12,880 | 2/2026 | Healthy | (Shaikh et al., 2009) |
| nsv523259 | CYP2C19 | Duplication | 159,144 | 1/2026 | Healthy | (Shaikh et al., 2009) |
| nsv1052578 | CYP2C19 | Deletion | 103,868 | 1/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| nsv1047782 | CYP2C19, CYP2C9 | Duplication | 137,386 | 1/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| esv2741937 | CYP2C19, CYP2C9 | Deletion | 138,826 | 1/96 | Healthy | (Wong et al., 2013) |
| esv3624265 | CYP2C9 | Duplication | 72,590 | 1/2504 | Healthy | (Genomes Project et al., 2015) |
| nsv551963 | CYP2C9 | Deletion | 23,682 | 1/15767 | Intellectual disability and/or developmental delay | (Cooper et al., 2011) |
| nsv7497 | CYP2C9 | Duplication | 34,308 | 1/8 | Healthy | (Kidd et al., 2008) |
| esv3624264 | CYP2C9, CYP2C8 | Duplication | 175,419 | 1/2504 | Healthy | (Genomes Project et al., 2015) |
| nsv1050544 | CYP2C8 | Duplication | 47,756 | 1/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| nsv1044182 | CYP2C8 | Duplication | 30,694 | 1/29084 | Intellectual disability and/or developmental delay | (Coe et al., 2014) |
| esv2761618 | CYP2C8 | Duplication | 30,682 | 1/1109 | Healthy | (Vogler et al., 2010) |
| nsv551964 | CYP2C8 | Deletion | 56,916 | 1/15767 | Intellectual disability and/or developmental delay | (Cooper et al., 2011) |
| nsv467436 | CYP2C8 | Deletion | 56,916 | 1/2493 | Healthy | (Itsara et al., 2009) |
| ClinGen | ||||||
| Pathogenic | ||||||
| nssv13651550_unk | 150 genes | Deletion | 7,901,553 | Behavioral abnormality, global development delay, microcephaly | (Miller et al., 2010) | |
| nssv13646178_unk | 2,161 genes | Duplication | 135,285,622 | Development delay and/or other significant development or morphological phenotypes | (Miller et al., 2010) | |
| nssv13638976_unk, nssv13640749_unk | 2,161 genes | Duplication | 135,327,117 | Abnormal facial shape, Intrauterine growth retardation, Micrognathia, Syndactyly, Ventricular septal defect | (Miller et al., 2010) | |
| nssv13655969_unk | 122 genes | Deletion | 6,302,504 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| nssv13655409_unk | 928 genes | Deletion | 53,839,386 | Global developmental delay | (Miller et al., 2010) | |
| nssv13653237_unk | 717 genes | Duplication | 42,143,651 | Patent ductus arteriosus | (Miller et al., 2010) | |
| nssv577306_dnovo | 109 genes | Deletion | 5,128,423 | Dilatation, Hydronephrosis | (Kaminsky et al., 2011) | |
| nssv577307_dnovo | 176 genes | Deletion | 8,175,579 | Abnormal facial shape | (Kaminsky et al., 2011) | |
| nssv1494941_unk | 54 genes | Deletion | 2,827,219 | Autism, Failure to thrive | (Miller et al., 2010) | |
| Benign | ||||||
| nssv581618_unk | CYP2C18, CYP2C19 | Deletion | 158,935 | Intellectual disability | (Miller et al., 2010) | |
| nssv1608783_unk | CYP2C19 | Deletion | 20,211 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| Likely Benign | ||||||
| nssv13650654_unk | CYP2C18, CYP2C19 | Deletion | 121,822 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| nssv13655256_unk | CYP2C18 | Deletion | 114,674 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| nssv13647268_unk | CYP2C19, CYP2C9 | Duplication | 180,257 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| nssv13650288_unk | CYP2C18 | Deletion | 48,162 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| nssv585041_unk | CYP2C18 | Deletion | 112,487 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| nssv13655998_unk | CYP2C8 | Duplication | 8,867 | Developmental delay and/or other significant developmental or morphological phenotypes | (Miller et al., 2010) | |
| Uncertain | ||||||
| nssv13650363_unk | CYP2C18, CYP2C19 | Deletion | 240,911 | Seizures | (Miller et al., 2010) | |
| nssv583937_pat | PLCE1, NOC3L, TBC1D12, HELLS, CYP2C18, CYP2C19, CYP2C9, CYP2C8, PDLM1, ACSM6 | Deletion | 969,724 | Low-set ears | (Miller et al., 2010) | |
| nssv580748_unk | CYP2C9, CYP2C8, PDLIM1, SORBS1 | Duplication | 473,822 | Global developmental delay | (Kaminsky et al., 2011) | |
| nssv1495397_unk | TBC1D12, HELLS, CYP2C18, CYP2C19, CYP2C9, CYP2C8, PDLIM1, SORBS1, ACSM6 | Duplication | 1,043,272 | Autistic behavior, Global developmental delay | (Miller et al., 2010) | |
| nssv3395040_unk | TBC1D12, HELLS, CYP2C18, CYP2C19, CYP2C9, CYP2C8, PDLIM1, SORBS1, ACSM6 | Duplication | 1,089,626 | Seizures | (Miller et al., 2010) | |
| DECIPHER | ||||||
| 184 | 175 genes | Deletion | 12,434,019 | Anterior creases of earlobe, capillary hemangiomas, hypoglycemia, intellectual disability, microcephaly | (Firth et al., 2009) | |
| 341717 | 122 genes | Duplication | 8,517,656 | Emotional lability, growth delay, intellectual disability | (Firth et al., 2009) | |
| 2578 | 232 genes | Duplication | 17,187,727 | Behavioral abnormality, constipation, deeply set eye, delayed speech and language development, intellectual disability, macrocephaly, pectus excavatum, plagiocephaly, short stature, ventricular septal defect | (Firth et al., 2009) | |
| 337109 | PLCE1, NOC3L, TBC1D12, HELLS, CYP2C18, CYP2C19, CYP2C9, CYP2C8, PDLIM1 | Duplication | 1,080,102 | Intellectual disability - moderate, oromotor apraxia, severe expressive language delay | (Firth et al., 2009) | |
| 292398 | PLCE1, NOC3L, TBC1D12, HELLS, CYP2C18, CYP2C19, CYP2C9, CYP2C8, PDLIM1 | Duplication | 1,080,102 | Anxiety, cognitive impairment | (Firth et al., 2009) | |
| 265438 | PLCE1, NOC3L, TBC1D12, HELLS, CYP2C18, CYP2C19, CYP2C9, CYP2C8, PDLIM1 | Duplication | 1,080,102 | - | (Firth et al., 2009) | |
| 260874 | PLCE1, NOC3L, TBC1D12, HELLS, CYP2C18, CYP2C19, CYP2C9, CYP2C8, PDLIM1 | Duplication | 1,080,102 | Delayed speech and language development, incomprehensible speech, intellectual disability - moderate, oromotor apraxia | (Firth et al., 2009) | |
| 318690 | CYP2C18, CYP2C19 | Deletion | 120,242 | Delayed speech and language development, EEG abnormality, moderate global developmental delay | (Firth et al., 2009) | |
| 300098 | CYP2C18, CYP2C19 | Deletion | 158,935 | Cognitive impairment | (Firth et al., 2009) | |
| 283724 | CYP2C18, CYP2C19 | Deletion | 140,797 | Abnormal facial shape, intellectual disability | (Firth et al., 2009) | |
| 278463 | CYP2C19 | Deletion | 61,682 | Behavioral abnormality | (Firth et al., 2009) | |
| 270359 | CYP2C19, CYP2C8, CYP2C9 | Duplication | 288,534 | Hypospadias, rudimentary fibula | (Firth et al., 2009) | |
| 256495 | 34 genes (CYP2C18 is not included) | Deletion | 2,093,635 | - | (Firth et al., 2009) | |
| 305972 | CYP2C19, CYP2C8, CYP2C9 | Duplication | 344,191 | - | (Firth et al., 2009) | |
| 272275 | CYP2C8, CYP2C9, PDLIM1, SORBS1 | Deletion | 694,656 | - | (Firth et al., 2009) | |