Radial dysplasia
Gene: RBM8A
Comment when marking as ready: Considered green as clear causation established, however mechanism is unusual as per: Comment on mode of inheritance: Vast majority are due to a recurrent 200kb deletion on one allele (although truncations are seen) and the presence of 1 of 2 SNPs in trans. The SNPs have a MAF of 3.05% and 0.42%. Information on the SNPs previously sent to Ellen Thomas, who forwarded to Olivia Niblock regarding the LabKey list of difficult variants.Created: 11 May 2017, 10:05 a.m.
Comment on mode of inheritance: Vast majority are due to a recurrent 200kb deletion on one allele (although truncations are seen) and the presence of 1 of 2 SNPs in trans. The SNPs have a MAF of 3.05% and 0.42%.Created: 28 Feb 2017, 1:57 p.m.
Recognised cause of thrombocytopaenia and absent radius however requires biallelic alterations. Above PMID (22366785) shows that a mutation on one allele (in the vast majority a recurrent 200kb deletion at 1q21 but one truncation and one frameshift mutation also seen) has to be inherited in trans with a SNP in the regulatory region on the other. In view of the presence of thrombocytopaenia alone, it is unlikely to be recruited via this panel, however discussion is needed about the ability to detect this condition given the deletion / SNP combination in the majority of cases. Amber at present.Created: 22 Feb 2017, 5:24 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Thrombocytopenia-absent radius syndrome 274000
Publications
RBM8A is on the panel for Radial dysplasia as an individual gene. In addition, UKGTN report a 200kb deletion for TAR syndrome, which removes 11 genes including RBM8A.Created: 13 Oct 2016, 10:59 a.m.
Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least four variants reportedCreated: 29 Jul 2016, 1:53 p.m.
Tier 2Created: 17 Jun 2016, 8:07 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Thrombocytopenia-absent radius syndrome 274000
Variants in this GENE are reported as part of current diagnostic practice
The UKGTN gene dossier explains that a 200kb deletion at 1q21.1 encompassing the genes; HFE2, TXNIP, PLOR3GL, ANKRD34A, LIX1L, RBM8A, GNRHR2, PEX11B, ITGA10, ANKRD35, PIAS3, NUDT1, is tested for diagnosis of Thrombocytopenia Absent-Radius Syndrome. "PLOR3GL" is likely to be POLR3GL, the correct spelling for this gene in this region.Created: 25 Jun 2015, 10:57 a.m.
23.05.2017: Panel revised and approved to Version 1.0 after expert review.
Phenotypes for RBM8A were set to Thrombocytopenia-absent radius syndrome, 274000
This gene has been classified as Green List (High Evidence).
Phenotypes for RBM8A were set to Thrombocytopenia-absent radius syndrome 274000
Publications for RBM8A were set to 22366785
RBM8A was added to Radial dysplasiapanel. Sources: Expert list
RBM8A was added to Radial dysplasiapanel. Source: UKGTN
RBM8A was added to Radial dysplasiapanel. Source: Emory Genetics Laboratory Model of inheritance for gene RBM8A was set to BIALLELIC, autosomal or pseudoautosomal
RBM8A was added to Radial dysplasiapanel. Source: Radboud University Medical Center, Nijmegen
RBM8A was created by rfoulger
RBM8A was added to Radial dysplasiapanel. Sources: Eligibility statement prior genetic testing