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Hereditary neuropathy NOT PMP22 copy number

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)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Djordjevic et al. 2021 (PMID:33417887) identified different de novo POLR3B variants in 6 unrelated individuals. EMG/NCSs for 5/6 individuals revealed predominantly demyelinating sensory and motor neuropathy. Other features included ID, ataxia, spasticity.

POLR3B is listed in G2P with a 'probable' disease confidence rating for this phenotype (POLR3B-related neurodevelopmental disorder - monoallelic), but is not yet in OMIM.

Overall, there is sufficient evidence to warrant a Green rating on this panel.
Created: 16 Jun 2021, 1:04 p.m. | Last Modified: 16 Jun 2021, 1:04 p.m.
Panel Version: 1.26

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Note biallelic variants cause a leukodystrophy.

New MOI and new phenotype reported in PMID: 33417887: Six unrelated individuals with de novo missense variants and ataxia, spasticity, variable intellectual disability and epilepsy, and predominantly demyelinating sensory motor peripheral neuropathy.
Protein modeling and proteomic analysis shows variants caused aberrant association of individual enzyme subunits rather than affecting overall enzyme assembly or stability.
Sources: Literature
Created: 1 Feb 2021, 10:50 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Ataxia, spasticity, and demyelinating neuropathy

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • 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 Ataxia, spasticity, and demyelinating neuropathy to POLR3B-related neurodevelopmental disorder; Ataxia, spasticity, and demyelinating neuropathy

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

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: POLR3B.

1 Feb 2021, 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 Hereditary neuropathy NOT PMP22 copy number. Sources: Literature Mode of inheritance for gene: POLR3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR3B were set to 33417887 Phenotypes for gene: POLR3B were set to Ataxia, spasticity, and demyelinating neuropathy Review for gene: POLR3B was set to GREEN