Table 1 Summary of ARHGAP35 variant and clinical data.
From: ARHGAP35 is a novel factor disrupted in human developmental eye phenotypes
Case number | Individual 1A | Individual 1B | Individual 2 | Individual 3 | Individual 4A | Individual 4B |
|---|---|---|---|---|---|---|
Inheritance | AD | Father of 1A | de novo | de novo | Inherited | Father of 4A |
Location (hg19) | 19:47503695-C- | 19:47503695-C- | 19:47503884-C- | 19:47423781-C-T | 19:47503739-T-C | 19:47503739-T-C |
Nucleotidea | c.4251delC | c.4251delC | c.4444delC | c.1849C > T | c.4294 T > C | c.4294 T > C |
Protein | p.(Thr1418Argfs*381) | p.(Thr1418Argfs*381) | p.(Gln1482Serfs*317) | p.(Arg617*) | p.(Cys1432Arg) | p.(Cys1432Arg) |
Location | End of Rho-GAP domain | End of Rho-GAP domain | C-terminal to Rho-GAP domain | pG1 domain | End of Rho-GAP domain | End of Rho-GAP domain |
Predicted effect | Truncation of normal protein in final exon and erroneous tail extension | Truncation of normal protein in final exon and erroneous tail extension | Truncation of normal protein in final exon and erroneous tail extension | Truncation in first exon | Missense in Rho-GAP domain | Missense in Rho-GAP domain |
CADD score | N/A | N/A | N/A | N/A | 32 | 32 |
REVEL score | N/A | N/A | N/A | N/A | 0.439 | 0.439 |
gnomADb | NP | NP | NP | NP | NP | NP |
Read depth NGS | 113/270 (42%) | 119/228 (52%) | 9/27 (33%) | 16/28 (57%) | 90/160 (56%) | 68/184 (37%) |
Sanger confirmed | Yes | Yes | Yes | No | Yes | Yes |
ACMG criteria | P: PVS1, PM2_supp, PP1 | P: PVS1, PM2_supp, PP1 | P: PVS1, PS2, PM2_supp | P: PVS1, PS2, PM2_supp | VUS: PM2, PP2, PP3 | VUS: PM2, PP2, PP3 |
Gender | Female | Male | Male | Male | Male | Male |
Age (y) | 27 | 68 | 2 | 3 | 42 | U |
Ocular | R severe microphthalmia with sclerocornea | L inferior iris, choroidal coloboma, cataract, microphthalmia, uveitis (30 y), retinal detachment; R diabetic retinopathy only | B Peters anomaly (type II) treated with k-pro | R microphthalmia, sclerocornea; L microphthalmia, iris hypoplasia, corectopia, B agenesis of optic nerves | B anophthalmia | Glasses from a young age but no MAC |
Craniofacial | B bifid tragus | – | Nevus flammeus of the glabella | – | – | – |
Development | WNL | WNL | WNL | Delayed: Nonambulatory at 27 m | WNL | WNL |
Cardiac | – | – | Pulmonary valve stenosis, thickened aortic leaflet | – | – | – |
Renal | – | – | Large L kidney with possible duplex anatomy | L duplicated ureters | – | – |
Cancer | – | Lymphoma at 38 y and 61 y | - | – | – | – |
Other | – | Type 2 IDDM; Hemangioma on R forearm | Nuchal cord at birth; Small capillary hemangioma on occiput | Macrocephaly likely related to a de novo PTEN variant chr10: 89624228 T > G | – | – |
