Table 2. Information on potentially deleterious variants identified per family.
Families are listed in alphabetical order by gene symbol.
| Family ID | Gene | NM number | Nucleotide change | Amino acid change | State | Evolutionary conservationa phastCons / phyloP | PP2 SIFT MT | CADD Score | EVSb | gnom ADc | HGMDd | Phenotypes | Segregation (M,P) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| B4212 | ATG2B | NM_018036.6 | c.2938G>A | p.Glu 980Lys |
het |
X. tropicalis 1.00 / 5.77 |
0.83 Del. / |
24.6 | NP | 0/4/280,668 | Gene | Lipomeningocele, tethered cord, neurogenic bladder, L VUR, neurogenic bowel, acrocyanosis | M: WT P: het |
| c.1246T>A | p.Ser 416Thr |
het |
X. tropicalis 1.00 / 4.92 |
0.98 Del. / |
23.7 | NP | NP | Gene | h: Het P: WT |
||||
| B4124 | EWSR1 | NM_013986.3 | c.13+4A>G | ess | Hom | / 0.99 / 2.15 | / | / | 0/1/2202 | 0/11/281,120 | Gene | Myelomeningocele, thoracolumbar, myelodysplasia, kyphoscoliosis and scoliosis, myelodysplastic syndrome, neurogenic bladder, neurogenic bowel, Chiari malformation type 2, hydrocephalus, intellectual disability, epilepsy, porencephaly, thrombocytopenia, | M: NA P: het |
| B4109 | GPR83 | NM_016540.3 | c.820G>C | p.Asp 274His |
het |
D. rerio 1.00 / 5.63 |
1.00 Del. D.C. |
24.2 | NP | NP | NP | Lipomyelomeningocele, neurogenic bladder BL VUR, neurogenic bowel, Chiari malformation type 2, hydrocephalus |
M: WT P: WT |
| B4271 | IGBP1 | NM_001551.2 | c.212T>C | p.Ile 71Thr |
hemi |
C. intestinalis 1.00 / 3.60 |
0.93 Del. D.C. |
26.4 | NP | NP | Gene | Myelomeningocele, neurogenic bladder, neurogenic bowel, Chiari malformation type 2, hydrocephalus, hip flexion contracture | M: het P: WT |
| B4104 | MAML1 | NM_014757.4 | c.202G>A | p.Ala 68Thr |
het |
D. rerio 1.00 / 4.56 |
0.99 Del. D.C. |
25 | NP | 0/5/101,280 | Gene | Myelomeningocele, neurogenic bladder, neurogenic bowel, Chiari malformation type 2, hydrocephalus, macrocephaly | M: het P: NA |
| c.1657G>A | p.Glu 553Lys |
het |
X. tropicalis 1.00 / 3.46 |
0.93 Del. D.C. |
24.4 | 0/16/ 4284 |
1/443/ 276,670 |
Gene | M: WT P: NA |
||||
| B4127 | MTMR8 | NM_017677.3 | c.866–2 A>G |
100% ESS |
hemi | / 1.00 / 1.84 | / | / | NP | 0/0/1/166,539 | Gene | Myelomeningocele, tethered spinal cord, neurogenic bladder PUV, BL hydronephrosis, neurogenic bowel, Chiari malformation type 2, corpus callosum agenesis, | M: het P: NA Sib: het |
| B4225 | MAGI3 | NM_0042782.1 | c.706C>G | p.Leu 236Val |
het |
X. tropicalis 1.00 / 4.03 |
0.13 Del. D.C. |
18.7 | 0/12/4,288 | 1/310/282,358 | Gene | Myelomeningocele, neurogenic bladder, Chiari malformation type 2, hydrocephalus | M: het P: NA |
| c.1786C>A | p.Pro 596Thr |
het |
D. rerio 1.00 / 5.74 |
0.99 Del. D.C. |
26.0 | NP | 0/1/251,442 | Gene | M: WT P: NA |
||||
| B4110 | NUP205 | NM_015135.2 | c.1218+4 delA |
ess | het | / 0.98 / 2.15 | / | / | 0/1/4,126 | 0/14/279,876 | Gene | Myelomeningocele, Neurogenic bladder, renal scar, neurogenic bowel, Chiari malformation type II, hydrocephalus, hypercholesterolemia | M: WT P: NA |
| c.5386C>T | p.Arg 1796Trp |
het |
X. tropicalis 0.99 / 0.24 |
0.99 Del. D.C. |
24.8 | NP | 0/25/282,834 | Gene | M: het P: NA |
||||
| B4144 | PIK3R4 | NM_014602.2 | c.1039C>T | p.Arg 347Trp |
hom |
D. rerio 1.00 / 2.75 |
0.63 Tol. D.C. |
27.6 | 0/14/4,286 | 0/369/282,816 | Gene | Myelomeningocele, scoliosis, neurogenic bladder, neurogenic bowel, Chiari malformation type 2, stenogyria, thinning of corpus callosum | M: het P: NA |
| B3893 | TSPEAR | NM_144991.2 | c.668C>T | p.Ser 223Leu |
hom |
D. rerio 1.00 / 5.47 |
0.52 Del. D.C. |
26.8 | 0/4/4,296 | 1/201/276,8820 | Gene | Myelomeningocele, neurogenic bladder, Chiari malformation type 2, hydrocephalus | M: NA P: NA |
| B4303 | TTC21A | NM_145755.2 | c.1416+1 G>A |
100% ESS |
het | / 1.00 / 5.55 | / | / | 0/13/4,140 | 0/100/279,732 | Gene | Myelomeningocele, scoliosis, neurogenic bladder, BL hydronephrosis, neurogenic bowel, Chiari malformation type 2, hydrocephalus, restrict lung disease | M: het P: NA |
| c.2910delA | p.Lys 970fs28 |
het | / 1.00 / 0.92 | / | / | 0/1/3,931 | 0/5/280,964 | Gene | M: WT P: NA |
||||
| B4194 | ZNF790 | NM_001242800.1 | c.964C>T | p.Arg 322* |
het | / 0.95 / 2.45 | / | / | 1/34/2,168 | 1/163/281,656 | Gene | Myelomeningocele, neurogenic bladder, neurogenic bowel, Chiari malformation type 2, coxa valga | M: het P: NA |
| c.904A>T | p.Arg 302* |
het | / 0.00 / −0.60 | / | / | NP | 0/1/314,06 | Gene | M: WT P: NA |
BL, bilateral; CADD, Combined Annotation Dependent Depletion (https://cadd.gs.washington.edu/); D.C., Disease Causing; Del., Deleterious; del; deletion, ESS, Essential Splice Site; ess, extended splice site; EVS, Exome Variant Server; fs, frameshift; gnomAD, Genome Aggregation Database; het, heterozygous; Hom, homozygous; hemi, hemizygous; L, left; M, Maternal; MT, Mutation Taster (http://www.mutationtaster.org); NA, not available; NP, not present; P, Paternal; PP2, PolyPhen 2 (http://genetics.bwh.harvard.edu/pph2); PUV, posterior urethral valve; RHD, renal/hypodysplasia; SIFT, Sorting intolerant from tolerant (http://sift.jcvi.org); Sib, sibling; Tol, tolerated; VUR, vesicoureteral reflux. WT, wildtype.
Evolutionary conservation was assessed across phylogeny: X. tropicalis, Xenopus tropicalis; D. rerio, Danio rerio; C. intestinalis, Ciona intestinalis.
Variant frequencies listed for homozygous/ hemizygous (if applicable)/ heterozygous/ total alleles detected in the population.
HGMD, (https://portal.biobaseinternational.com/hgmd). If the exact variant has previously been reported and classified as a pathogenic mutation to be disease causing, variant denoted as “DM”. If the gene but not the exact variant has been reported for the corresponding phenotype “Gene” is indicated.