Fetal anomalies
Gene: GNB2

GNB2 (G protein subunit beta 2)
EnsemblGeneIds (GRCh38): ENSG00000172354
EnsemblGeneIds (GRCh37): ENSG00000172354
OMIM: 139390, Gene2Phenotype
GNB2 is in 5 panels

3 reviews

Natalie Canham (Liverpool Women's Hospital)

Green List (high evidence)

14 independent patients over three papers, cardiac and renal anomalies reported, most variants are recurrent.
Created: 20 Feb 2025, 9:35 p.m. | Last Modified: 20 Feb 2025, 9:35 p.m.

Panel Version: 5.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder with hypotonia and dysmorphic facies, MIM#619503

Publications

Created: 20 Feb 2025, 9:35 p.m.
Last Modified: 20 Feb 2025, 9:35 p.m.
Panel version: 5.15

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 25 Feb 2025, 11:15 a.m. | Last Modified: 25 Feb 2025, 11:15 a.m.

Panel Version: 5.78

This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Created: 20 Feb 2025, 9:40 p.m. | Last Modified: 20 Feb 2025, 9:40 p.m.

Panel Version: 5.16

Comment on list classification: As reviewed by Sarah Graham, monoallelic GNB2 variants are associated with a neurodevelopmental disorder with features including dysmorphic facial features, cardiac and renal abnormalities.

This gene has been associated with phenotypes in OMIM (MIM #619503) and DD panel of Gene2Phenotype resource (with 'Definitive' rating, previously known as 'confirmed').

A foetus was also reported with phenotypes consistent with this gene.

Hence, this gene can be promoted to green rating in the next GMS update.
Created: 26 Jun 2024, 10:56 a.m. | Last Modified: 26 Jun 2024, 10:56 a.m.

Panel Version: 4.12

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder with hypotonia and dysmorphic facies, OMIM:619503

Publications

Created: 26 Jun 2024, 10:47 a.m.
Last Modified: 26 Jun 2024, 10:47 a.m.
Panel version: 5.78

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

Gene associated with autosomal dominant neurodevelopmental disorder; features include dysmorphic facial features, cardiac and renal abnormalities (OMIM #619503). Recurrent de novo pathogenic missense variant p.(Lys89Glu) (https://www.ncbi.nlm.nih.gov/clinvar/variation/1217306/) reported in a fetus with phenotype consistent with this gene: cardiac abnormalities (hypoplastic left heart and hypoplastic aortic arch, double outlet right ventricle, great arteries located side-by-side, ventricular septal defect, persistent left superior vena cava connecting to coronary sinus), renal agenesis, mildly dysmorphic facies (Byrne 2023 PMID: 36658419).
Sources: Literature
Created: 15 Jun 2024, 11:54 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

36658419

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Created: 15 Jun 2024, 11:54 a.m.

Panel version: 4.3

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS

Phenotypes

Neurodevelopmental disorder with hypotonia and dysmorphic facies, OMIM:619503

OMIM

139390

Clinvar variants

Variants in GNB2

Penetrance

None

Publications

Mode of Pathogenicity

Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Panels with this gene