Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: POLR3B

Amber List (moderate evidence)

POLR3B (RNA polymerase III subunit B)
EnsemblGeneIds (GRCh38): ENSG00000013503
EnsemblGeneIds (GRCh37): ENSG00000013503
OMIM: 614366, Gene2Phenotype
POLR3B is in 9 panels

2 reviews

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

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

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381
  • POLR3B-related neurodevelopmental disorder
  • Ataxia, spasticity, and demyelinating neuropathy
Tags
Q2_21_rating
OMIM
614366
Clinvar variants
Variants in POLR3B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

16 Jun 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381 to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381; POLR3B-related neurodevelopmental disorder; Ataxia, spasticity, and demyelinating neuropathy

16 Jun 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: POLR3B.

16 Jun 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: POLR3B were set to 22036171; 22036172

16 Jun 2021, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: POLR3B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

16 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: polr3b has been classified as Amber List (Moderate Evidence).

16 Jun 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: POLR3B were changed from Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381 to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM:614381

12 Sep 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: POLR3B was added gene: POLR3B was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3B were set to 22036171; 22036172 Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381 Review for gene: POLR3B was set to GREEN gene: POLR3B was marked as current diagnostic