Intellectual disability
Gene: TRA2B

TRA2B (transformer 2 beta homolog)
EnsemblGeneIds (GRCh38): ENSG00000136527
EnsemblGeneIds (GRCh37): ENSG00000136527
OMIM: 602719, Gene2Phenotype
TRA2B is in 4 panels

3 reviews

Eleanor Williams (Genomics England Curator)

This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:36549593 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag
Created: 16 Oct 2023, 8:13 p.m. | Last Modified: 16 Oct 2023, 8:13 p.m.

Panel Version: 5.313

Created: 16 Oct 2023, 8:13 p.m.
Last Modified: 16 Oct 2023, 8:13 p.m.
Panel version: 5.313

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.

Panel Version: 5.286

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 11 Oct 2023, 9:34 a.m.
Last Modified: 11 Oct 2023, 9:34 a.m.
Panel version: 5.286

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Created: 1 Jun 2023, 3:14 p.m. | Last Modified: 1 Jun 2023, 3:14 p.m.

Panel Version: 5.174

PMID:36549593 reported 12 individuals from 11 unrelated families identified with 11 different heterozygous variants in TRA2B gene. The variants arose de novo in 10 families, while the variant was inherited from father to son in one family. 6 variants were expected to disrupt the translation start site in exon 1 (start-loss variants), 3 were expected to disrupt the splicing process at the exon 2/3 boundary (splice-affecting variants), and the remaining 2 were expected to produce a premature stop codon (truncating variants).

These patients presented with a neurodevelopmental disorder comprising developmental delay/ intellectual disability (in all patients), axial or global hypotonia (10 patients), delayed motor milestones (all patients), behavioural issues (8 patients), speech impairment (9 patients), epilepsy (7 patients, initial presentation as infantile spasms in 6 and unclassified epileptic encephalopathy in 1), brain abnormalities (10 patients) and microcephaly (5 patients). The degree of ID was severe to profound for 6 individuals, moderate to severe for 2 and mild to moderate for 3.

In addition, functional studies in mice showed that heterozygous knockout mice developed normal, while complete knockout mice cannot develop embryonically.

This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Created: 1 Jun 2023, 2:48 p.m. | Last Modified: 1 Jun 2023, 3:10 p.m.

Panel Version: 5.171

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

36549593

Created: 1 Jun 2023, 2:48 p.m.
Last Modified: 1 Jun 2023, 3:10 p.m.
Panel version: 5.171

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS
Literature

Phenotypes

neurodevelopmental disorder, MONDO:0700092
intellectual disability, MONDO:0001071

Tags

gene-checked

OMIM

602719

Clinvar variants

Variants in TRA2B

Penetrance

None

Publications

36549593

Panels with this gene

History Filter Activity

16 Oct 2023, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag gene-checked tag was added to gene: TRA2B.

11 Oct 2023, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_23_promote_green was removed from gene: TRA2B.

11 Oct 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to TRA2B. Source Expert Review Green was added to TRA2B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

1 Jun 2023, Gel status: 2