Table 1 Details of selected positive cases (cases for which copy number variant analysis of exome sequencing data yielded a pathogenic or likely pathogenic result)
Case | ISCN array or HGVS nomenclature (hg19) | Size (KB) | # Genes | Exome type | Inheritance | OMIM gene(s) | Exons | Phenotype | ACMG/ClinGen classification codes | CNV classification |
|---|---|---|---|---|---|---|---|---|---|---|
Exonic or Gene-level Deletions | ||||||||||
1 | 12q21.2(80186886_80194010)x1 dn | 7.1 | 1 | Trio | De novo | PPP1R12A | 16–20 | Infantile spasms, microcephaly, developmental delay, and osteopenia | 1 A(0) + 2E(0.9) + 3 A(0) + 4 C(0.15) = 1.05 | Pathogenic |
2 | 12q21.33(89853261_89871860)x1 mat | 18.6 | 1 | Quad | Maternal | POC1B | 4–9 | Retinal disorder and multiple congenital anomalies | 1 A(0) + 2E(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
c.676+1 G > A (p.?) | - | - | Paternal | POC1B | Intron 6 | not applicable | Not applicable | |||
3 | 11p12(36619654_36619829)x1 | 0.2 | 1 | Singleton | Unknown | RAG2 | 1 | Immunodeficiency- neonatal | 1 A(0) + 2 C(0.45) + 4 A(0.45) = 0.9 | Likely pathogenic |
c.685 C > T (p.Arg229Trp) | - | - | - | Unknown | RAG2 | 2 | not applicable | Not applicable | ||
4 | 6q24.3(146007252_146007437)x0 | 0.2 | 1 | Quad | Maternal and paternal | EPM2A | 2 | Seizures | 1 A(0) + 2E(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
5 | 1p31.3(65270424_65325984)x1 | 55.6 | 1 | Singleton | Maternal | JAK1 | 9–25 | Immunodeficiency, multiple congenital anomalies- neonatal | 1 A(0) + 2E(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
c.1613dupT (p.Met539Hisfs*21) | - | - | - | Paternal | JAK1 | 11 | not applicable | Not applicable | ||
6 | 4p13(41727326_41766550)x1 | 39.2 | 1 | Trio | Maternal | PHOX2B | Whole gene | Congenital central hypoventilation syndrome, Hirschsprung disease, cancer | 1 A(0) + 2 A(1) + 3 A(0) = 1.0 | Pathogenic |
7 | 10q25.1(105832424_105839436)x1 | 6.5 | 1 | Singleton | Unknown | COL17A1 | 3–7 | Epidermolysis bullosa | 1 A(0) + 2E(0.45) + 4 A(0.45) = 0.9 | Likely pathogenic |
c.4145_4148delAGAG (p.Glu1382Alafs*40) | - | - | - | Unknown | COL17A1 | 52 | not applicable | Not applicable | ||
8 | Xq26.3(135077105_135106429)x0 | 25 | 1 | Singleton | Unknown | SLC9A6 | 3–11 | Microcephaly, hypotonia, developmental delay | 1 A(0) + 2E(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
9 | 1q22(155261544_155261729)x0 | 0.2 | 1 | Singleton | Unknown | PKLR | 10 | Hemolytic anemia | 1 A(0) + 2E(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
10 | 19p13.2(13416091_13423501)x1 | 7.4 | 1 | Singleton | Unknown | CACNA1A | 12–15 | Seizures, microcephaly, hypotonia and developmental delay | 1A(0) + 2E(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
11 | 6p21.33(31948808_32013078)x1 | 64.3 | 2 | Singleton | Unknown | CYP21 A2, TNXB | Whole gene | Congenital adrenal hyperplasia | 1A(0) + 2 A(1) + 3 A(0) = 1.0 | Pathogenic |
12 | 16q23.1(78245579_78264783)x1, 16q23.1(78264901_78458625)x0, 16q23.1(78458626_78626250)x1 | 19.2, 193.7, 167.6 | 1 | Singleton | Unknown | WWOX | 6 | Infantile spasms, ocular disorder | 1 A(0) + 2E(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
13 | 4q12(57766301_57786025)x1 | 19.7 | 1 | Singleton | Unknown | REST | 1–3 | Hemolytic anemia; history of Wilm’s tumor | 1 A(0) + 2C-1(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
14 | 22q11.21(20030809_20061408)x0 | 30.6 | 1 | Duo | Maternal (mother: heterozygous carrier) | TANGO2 | 3–9 | MELAS-like syndrome | 1 A(0) + 2D(0.9) + 3 A(0) + 4 L(0.15) = 1.05 | Pathogenic |
15 | 11p11.2(44126323_44130858)x1 | 4.5 | 1 | Singleton | Unknown | EXT2 | 2–3 | Multiple exostoses | 1 A(0) + 2C-1(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
16 | 7q36.3(156786857_156809656)x1 | 22.8 | 1 | Singleton | Unknown | MNX1 | Whole gene | Anogenital and spinal anomalies | 1 A(0) + 2 A(1) + 3 A(0) = 1.0 | Pathogenic |
17 | 10q22.3(81066056-81073780)x1 | 7.7 | 1 | Singleton | Unknown | ZMIZ1 | 22–25 | Multiple musculoskeletal anomalies | 1 A(0) + 2D-4(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
18 | Xq13.1(68907857_69192664)x0 | 285 | 1 | Singleton | Unknown | EDA | 2 | Anhidrosis | 1 A(0) + 2 A(1) + 3 A(0) = 1.0 | Pathogenic |
19 | 17q22(56778978_56824455)x1 | 45.5 | 1 | Singleton | Unknown | RAD51C | 4–9 | Neurodevelopmental delays, seizures, abnormal brain MRI findings | 1 A(0) + 2D-4(0.9) + 3 A(0) = 0.9 | Likely pathogenic |
20 | 17q21.31(41234581_41249619)x1 | 15 | 1 | Trio | Paternal | BRCA1 | 8–12 | Hydrocephalus, macrocephaly, ventriculomegaly, global developmental delay, paternal family history of cancer | 1 A(0) + 2E(0.9) + 3 A(0) + 4 L(0.15) = 1.05 | Pathogenic |
Deletions (≤10 Mb) | ||||||||||
21 | 16q23.3q24.1(83823068_86020801)x1 dn | 2197.7 | 38 | Trio | De novo, maternal allele affected | - | - | Respiratory insufficiency and pulmonary hypertension | 1 A(0) + 2 A(1) + 3B(0.45) + 4 A(0.45) + 4 L(0.15) = 2.05 | Pathogenic |
22 | 19p13.3(3834392_4793716)x1 | 959.3 | 36 | Trio | De novo | - | - | Immunodeficiency and multiple congenital anomalies | 1 A(0) + 2 A(1) + 3B(0.45) + 4 C(0.15) + 4 L(0.15) = 1.75 | Pathogenic |
23 | 1p32.1p31.3(59362523_66962272)x1 | 7599.8 | 52 | Singleton | Unknown | - | - | Macrocephaly and feeding difficulties | 1 A(0) + 2 A(1) + 3B(0.45) + 4 L(0.15) = 1.6 | Pathogenic |
24 | 2q24.3q31.1(165697586_170497735)x1 | 4800.2 | 33 | Singleton | Unknown | - | - | Seizures | 1 A(0) + 2 A(1) + 3B(0.45) + 4 L(0.15) = 1.6 | Pathogenic |
25 | 22q11.21(18736983_21399971)x1 | 2663 | 77 | Trio | De novo | - | - | Suspected 22q11.2 deletion syndrome | 1 A(0) + 2 A(1) + 3 C(0.9) + 4B(0.3) + 4 L(0.15) = 2.35 | Pathogenic |
26 | 11p11.2(45831196_47848758)x1 | 2017.6 | 51 | Singleton | Unknown | - | - | Developmental delay, hypotonia, and skull abnormalities | 1 A(0) + 2 A(1) + 3 C(0.9) = 1.9 | Pathogenic |
27 | Xq23q24(114703580_116953429)x0 | 2249.9 | 8 | Singleton | Unknown | - | - | Osteoporosis | 1 A(0) + 2 A(1) + 3 A(0.0) = 1.0 | Pathogenic |
28 | 16q23.3q24.1(84046426_86401800)x1 dn | 2355.4 | 36 | Trio | De novo, maternal allele affected | - | - | Respiratory failure - neonate | 1 A(0) + 2 A(1) + 3 A(0.0) + 4 A(0.45) + 4 L(0.15) = 1.6 | Pathogenic |
29 | 1q24.3q25.2(171494199_177333098)x1 dn | 5838.9 | 60 | Trio | De novo | - | - | Short stature and multiple congenital anomalies | 1 A(0) + 2 A(1) + 3B(0.45) + 4 A(0.15) + 4 L(0.15) = 1.75 | Pathogenic |
30 | 8p23.1(7077836_12453049)x1 dn | 5375.2 | 92 | Trio | De novo | - | - | Multiple congenital anomalies - neonate | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 C(0.15) + 4 L(0.15) = 2.2 | Pathogenic |
31 | 8q12.1q12.2(60883137_62020511)x1 | 1137.4 | 5 | Singleton | Unknown | - | - | CHARGE syndrome | 1 A(0) + 2 A(1) + 3 A(0.0) = 1.0 | Pathogenic |
32 | 11p14.3p14.1(25876609_30386283)x1 dn | 4509.7 | 24 | Trio | De novo | - | - | Seizures, hypotonia, developmental delay, multiple congenital anomalies | 1 A(0) + 2 A(0.75) + 3 A(0.0) + 4 C(0.15) = 0.9 | Likely pathogenic |
33 | 1q24.2q25.1(170629149_175296623)x1 dn | 4667.5 | 61 | Trio | De novo | - | - | Congenital heart disease, central nervous system and lung abnormalities | 1 A(0) + 2 A(1) + 3B(0.45) + 4 A(0.15) + 4 L(0.15) = 1.75 | Pathogenic |
34 | 15q11.2q13.1(23609259_28556183)x1 | 4946.9 | 113 | Singleton | Unknown | - | - | Craniofacial dysostosis, developmental delay, and obesity | 1 A(0) + 2 A(1) + 3 A(0.0) + 4 L(0.15) = 1.15 | Pathogenic |
35 | 22q11.21(18873934_20329008)x1, 22q11.21(20691108_21414783)x1 | 1455.1, 723.7 | 47, 22 | Singleton | Unknown | - | - | Velocardiofacial syndrome | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 L(0.15) = 2.05 | Pathogenic |
36 | 22q11.21(18836133_20378733)x1 dn, 22q11.21(20716609_21696333)x1 dn | 1542.6, 979.7 | 51, 28 | Trio | De novo | - | - | Failure to thrive, congenital heart disease, and metabolic acidosis | 1 A(0) + 2 A(1) + 3 C(0.9) + 4B(0.3) + 4 L(0.15) = 2.35 | Pathogenic |
37 | 8q21.3q22.1(88375006_96019455)x1 dn | 7644.5 | 51 | Trio | De novo | - | - | Multiple Congenital anomalies | 1 A(0) + 2 A(1) + 3B(0.45) + 4 C(0.15) + 4 L(0.15) = 1.75 | Pathogenic |
38 | 15q11.2(22770422_23191651)x1 | 421.2 | 6 | Trio | Maternal | - | Microcephaly, hepatosplenomegaly, hepatic and renal calcifications, thrombocytopenia, anemia | 1 A(0) + 2 A(1) + 3 A(0.0) + 4 L(0.05) = 2.05 | Pathogenic | |
39 | 16p11.2(28822635-29046499)x1 | 223.9 | 9 | Singleton | Unknown | Renal failure | 1 A(0) + 2 A(1) + 3 A(0.0) + 4 L(0.15) = 1.15 | Pathogenic | ||
Duplications (≤10 Mb) | ||||||||||
40 | 15q22.31q23(66091359_69348983)x3 | 3257.6 | 43 | Singleton | Unknown | - | - | Epilepsy | 1 A(0) + 2H(0.0) + 3B(0.45) + 4 C(0.3) + 4E(0.15) = 0.9 | Likely pathogenic |
41 | 8p23.1(11152812_11985611)x3 dn | 832.8 | 21 | Trio | De novo | - | - | Congenital heart disease | 1 A(0) + 2 A(0.45) + 3 A(0.0) + 4 A(0.45) = 0.9 | Likely pathogenic |
42 | 8p23.1(9599237_12031061)x3 pat | 2431.8 | 42 | Trio | Paternal | - | - | Congenital heart disease | 1 A(0) + 2 A(0.45) + 3 A(0.0) + 3B(0.45) + 4 K(-0.15) + 4 L(0.15) = 0.9 | Likely pathogenic |
Large (>10 Mb) and Complex CNVs | ||||||||||
43 | 2q24.1q24.3(154742487_168107786)x1 | 13365.3 | 71 | Singleton | Unknown | - | - | Seizures and developmental delay | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 L(0.15) = 2.05 | Pathogenic |
44 | 13q14.11q14.3(43642976_54529864)x1 | 10886.9 | 119 | Singleton | Unknown | - | - | Thrombocytopenia, cancer, developmental delay | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 L(0.15) = 1.75 | Pathogenic |
45 | 18p11.32p11.21(117412_15365910)x1 | 15248.5 | - | Singleton | Unknown | - | - | Multiple congenital anomalies | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 L(0.15) = 2.05 | Pathogenic |
46 | 11p15.5(1_637689)x1, 11q22.3q25(107521458_135006516)x3 | 637.7, 27485.1 | - | Singleton | Unknown | - | - | Multiple congenital anomalies and hypoglycemia | 1 A(0) + 2 A(1) + 3 A(0.0) = 1.0, 1 A(0) + 2H(0.0) + 3 C(0.9) = 0.9 | Pathogenic, Likely pathogenic |
47 | 18p11.32(1_402485)x1, 18q21.32q23(57714711_78077248)x1 | 402.5, 20362.5 | - | Singleton | Unknown | - | - | Multiple congenital anomalies and iron deficiency | Not applicable | Pathogenic due to expected ring chromosome |
48 | 18p11.32p11.21(48261_13786460)x1 | 13738.2 | - | Singleton | Unknown | - | - | Infantile spasms | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 L(0.15) = 2.05 | Pathogenic |
49 | 13q31.3q34(93518602_115169878)x1 | 21651.3 | - | Singleton | Unknown | - | - | Multiple congenital anomalies and coagulation abnormality | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 L(0.15) = 2.05 | Pathogenic |
50 | 11q23.3q24.1(119103408_121440633)x4, 11q24.1q25(121508159_134356983)x2 hmz | 2337.2, 12848.8 | - | Singleton | Unknown | - | - | Central nervous system abnormalities and hypoplastic aortic arch | 1 A(0) + 2 K(0.45) + 3B(0.45) + 3 C(0.0) = 0.9 | Likely pathogenic |
51 | 10p15.3p13(95137_12223086)x1, 13q34(113408715_115169878)x3 | 12127.9, 1761.2 | - | Singleton | Unknown | - | - | Cystic kidney dysplasia, hearing loss, multiple congenital anomalies | 1 A(0) + 2 A(1) + 3 C(0.9) + 4 L(0.15) = 2.05, 1 A(0) + 2H(0.0) + 3 A(0.0) + 4 L(0.15) = 0.15 | Pathogenic, predicted unbalanced translocation |
Aneuploidy | ||||||||||
52 | Trisomy 21 | - | - | Singleton | Unknown | - | - | Multiple congenital anomalies | Well established, not applicable | Not applicable |
53 | Trisomy 21 | - | - | Singleton | Unknown | - | - | Multiple congenital anomalies | Well established, not applicable | Not applicable |
54 | Trisomy 21 | - | - | Singleton | Unknown | - | - | Multiple congenital anomalies | Well established, not applicable | Not applicable |
55 | Trisomy 21 | - | - | Singleton | Unknown | - | - | Multiple congenital anomalies | Well established, not applicable | Not applicable |
56 | XXY | - | - | Singleton | Unknown | - | - | Connective tissue abnormalities | Well established, not applicable | Not applicable |
57 | Trisomy 21 | - | - | Singleton | Unknown | - | - | Multiple congenital anomalies | Well established, not applicable | Not applicable |
58 | XXY | - | - | Singleton | Unknown | - | - | Recurrent pancreatitis, diabetes, and obesity | Well established, not applicable | Not applicable |
59 | Trisomy 21 | - | - | Singleton | Unknown | - | - | Multiple congenital anomalies and immunodeficiency | Well established, not applicable | Not applicable |
60 | Trisomy 21 | - | - | Trio | De novo, maternal allele affected | - | - | Multiple congenital anomalies; cystic kidney dysplasia | Well established, not applicable | Not applicable |
61 | Monosomy X | - | - | Singleton | Unknown | - | - | Congenital heart disease | Well established, not applicable | Not applicable |
Absence of Heterozygosity and Mosaic Findings | ||||||||||
62 | 17p13.3p11.2 ×2 hmz | - | - | Trio | - | - | - | Multiple congenital anomalies, clinical remission of AML | Somatic alteration, not applicable | Not applicable |
63 | Whole genome UPD | - | - | Trio | - | - | - | Hemihypertrophy and renal cyst | Whole-genome UPD, not applicable | Not applicable |
64 | mos(7)x1, 12p13.2p12.1(10733285_22482185)x1 | 159138.7, 11748.9 | - | Singleton | - | - | - | Myelodysplastic syndrome | Somatic alteration, not applicable | Not applicable |
