Skeletal dysplasiaGene: UBA2
Comment on list classification: Promoting this gene from grey to amber as there are two cases with SNVs reported.
Created: 20 Jan 2021, 5:23 p.m. | Last Modified: 20 Jan 2021, 5:23 p.m.
Panel Version: 2.56
As the reviewer notes there are two reports on SNV in UBA2 in patients with split-hand/foot malformation. There are also reports of microdeletions including the UBA2 gene in 2 patients with split-hand/foot malformation/ectrodactyly
PMID: 31332306 - Yamoto et al 2019 - report one Japanese patient (38-II-1) with split-hand/foot malformation and a de novo c.1324dupT p.(Tyr442Leufs17) variant in UBA2 was found by exome sequencing. Not found in gnomAD. The UBA2 gene was considered a candidate gene because deletion of the region containing this gene (19q13.11) was found in a SHFM patient in this study using aCGH (patient 26-II-3) and in two other studies where microdeletions encompassing the UBA2 gene (among many other genes) were found in singular patients with ectrodactyly; PMID: 24243649 Chowdhury et al 2013 and PMID: 29988626 Abe et al 2019.
PMID: 31587267 - mother and son with aplasia cutis congenita. The son also has bilateral ectrodactyly, a horseshoe kidney, low‐lying conus medullaris and tracheo‐oesophageal fistula. WES identified a heterozygous deletion at c.327delT of UBA2, which leads to a frameshift and early top codon, in both the son and his mother.
Created: 20 Jan 2021, 5:20 p.m. | Last Modified: 20 Jan 2021, 5:20 p.m.
Panel Version: 2.55
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
split hand-foot malformation MONDO:0016576; aplasia cutis congenita (disease) MONDO:0007145; ectrodactyly
PMID: 31332306 - a single individual with a de novo PTC and split hand/foot malformation (SHFM). Additional two multigenic CNVs including this gene in individuals with SHFM and ectrodactyly. Authors mention an additional de novo missense but the patient didnt have SHFM, argue low penetrance PMID: 31587267 - a mother and son with aplasia cutis congenita (ACC), with a heterozygous PTC. Son also has ectrodactyly. Authors note an additional de novo missense in a patient with ACC.
Created: 1 May 2020, 9:50 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to split hand-foot malformation MONDO:0016576; aplasia cutis congenita (disease) MONDO:0007145; Ectrodactyly
Publications for gene: UBA2 were set to 31332306; 31587267
Gene: uba2 has been classified as Amber List (Moderate Evidence).
gene: UBA2 was added gene: UBA2 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UBA2 were set to 31332306; 31587267 Phenotypes for gene: UBA2 were set to Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly Review for gene: UBA2 was set to AMBER