Ataxia and cerebellar anomalies - narrow panel
Gene: POLR3B

POLR3B (RNA polymerase III subunit B)
EnsemblGeneIds (GRCh38): ENSG00000013503
EnsemblGeneIds (GRCh37): ENSG00000013503
OMIM: 614366, Gene2Phenotype
POLR3B is in 8 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.

Panel Version: 3.30

Created: 5 Feb 2023, 5:18 p.m.
Last Modified: 5 Feb 2023, 5:18 p.m.
Panel version: 3.30

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Progressive childhood-onset cerebellar ataxia is a feature in a subset of cases with biallelic variants in this gene. There are sufficient unrelated families in literature to warrant a Green rating on this panel (>10 individuals reported with ataxia)

Recently, heterozygous variants were also linked to ataxia, with different de novo POLR3B variants identified in 6 unrelated individuals (PMID:33417887). All had had a variable degree of gait dysfunction - 5/6 had truncal and/or appendicular ataxia with wide-based ataxic gait, inability to perform tandem gait, or gait instability. Protein modelling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.

Comment on mode of inheritance: Both biallelic and monoallelic variants have been linked to ataxia - enough evidence for a Green rating for both allelic requirements
Created: 16 Jun 2021, 11:25 a.m. | Last Modified: 16 Jun 2021, 11:30 a.m.

Panel Version: 2.197

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 16 Jun 2021, 11:25 a.m.
Last Modified: 16 Jun 2021, 11:30 a.m.
Panel version: 2.197

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Ataxia is a presenting feature.
Sources: Expert list
Created: 12 Sep 2020, 6:51 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 12 Sep 2020, 6:51 a.m.

Panel version: 2.12

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

NHS GMS
Expert Review Green

Phenotypes

Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381
POLR3B-related neurodevelopmental disorder
Ataxia, spasticity, and demyelinating neuropathy

OMIM

614366

Clinvar variants

Variants in POLR3B

Penetrance

None

Publications

Panels with this gene

History Filter Activity

5 Feb 2023, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: POLR3B.

5 Feb 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source Expert Review Green was added to POLR3B. Source NHS GMS was added to POLR3B. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

16 Jun 2021, Gel status: 2