Table 4.

DGAP239, DGAP247, DGAP248 and DGAP258: Significant Protein-Coding Genes Surrounding the Breakpoints according to TADs and Convergent Genomic Evidence

Gene	Nucleotides (GRCh37/hg19)	Description	OMIM37	OMIM Morbid37	DDG2P39	HI (%)36	Notes
DGAP239: 6q13 Breakpoints on Rearrangement_A (70,405,86{7-8}) and Rearrangement_B (70,405,86{7-9})
ADGRB3	69,345,259–70,099,403	adhesion G protein-coupled receptor B3	602684	−	−	3.02	no reported phenotype association; homologous to ADGRB1, an angiogenesis inhibitor that is a candidate for involvement in development of glioblastoma41
LMBRD1 (disrupted)	70,385,694–70,507,003	LMBR1 domain containing 1	612625	+	+	12.92	biallelic loss of function (autosomal recessive) associated with methylmalonic aciduria and homocystinuria, cblF type42 (no phenotypic overlap with DGAP239)
DGAP239: 8q12.2 Breakpoints on Rearrangement_A (61,628,67{1-2}) and Rearrangement_B (61,628,66{7-9})
CHD7 (disrupted)	61,591,337–61,779,465	chromodomain helicase DNA binding protein 7	608892	+	+	2.4	haploinsufficiency (autosomal dominant, monoallelic) reported to be associated with CHARGE syndrome, such that mutations in >90% of subjects meet diagnostic criteria of CHARGE syndrome43 (consistent with the clinical diagnosis of CHARGE syndrome during the postnatal period of DGAP239)
DGAP247: 8q11.2 Breakpoints on Rearrangement_A (51,889,501) and Rearrangement_B (51,889,502)
No significant gene within the same TAD as the breakpoints
DGAP247: 8q24.23 Breakpoints on Rearrangement_A (136,495,820) and Rearrangement_B (136,495,823)
KHDRBS3	136,469,700–136,668,965	KH domain containing, RNA binding, signal transduction associated 3	610421	−	−	10.52	no reported phenotype association
DGAP248: 2p12 Breakpoints on Rearrangement_A (78,301,91{1-2}) and Rearrangement_B (78,301,90{8-5})
LRRTM4	76,974,845–77,820,445	leucine rich repeat transmembrane neuronal 4	610870	−	−	7.26	no reported phenotype association; structure and expression profile of LRRTM mRNAs in mice suggest role in development and maintenance of the vertebrate nervous system44
DGAP248: 13q13.2 breakpoints on Rearrangement_A (34,542,73{2-1}) and Rearrangement_B (34,542,7{20-23})
RFC3 (disrupted)	34,392,186–34,540,695	replication factor C subunit 3	600405	−	−	4.93	no reported phenotype association
NBEA	35,516,424–36,247,159	neurobeachin	6084889	−	−	6.83	disrupted in a subject with a de novo translocation and idiopathic autism,45 and haploinsufficiency causes autism-like behaviors in animal models46, 47
DGAP258: 6p25.3 Breakpoints on Rearrangement_A (776,81{6}) and Rearrangement_B (776,787)
No significant gene within the same TAD as the breakpoints
DGAP258: 6q16.1 Breakpoints on Rearrangement_A (93,191,54{7}) and Rearrangement_B (93,191,545)
MAP3K7	91,223,292–91,296,764	mitogen-activated protein kinase kinase kinase 7	602614	−	−	2.75	no reported phenotype association

Abbreviations are as follows: DDG2P, Developmental Disorders Genotype-to-Phenotype database; and HI, haploinsufficiency index.