Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: UBTF

Amber List (moderate evidence)

UBTF (upstream binding transcription factor, RNA polymerase I)
EnsemblGeneIds (GRCh38): ENSG00000108312
EnsemblGeneIds (GRCh37): ENSG00000108312
OMIM: 600673, Gene2Phenotype
UBTF is in 6 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 9 unrelated individuals from different ethnic backgrounds in literature with neuroregression including ataxia as an early feature due to a recurrent variant in this gene (PMIDs: 28777933; 29300972; 30517966; 31931739)
Created: 6 May 2021, 3:47 p.m. | Last Modified: 6 May 2021, 3:47 p.m.
Panel Version: 2.159
UBTF is associated with a relevant phenotype in OMIM and has a 'probable' disease confidence rating for 'Childhood-Onset Neurodegeneration' ​in Gene2Phenotype.

- PMID: 28777933 (2017) - 7 unrelated individuals with developmental regression starting at 2.5–7 years and the same de novo heterozygous variant, (c.628G>A, p.Glu210Lys) in UBTF. Variable movement phenotype were observed including ataxia in 3/7 subjects.

- PMID: 29300972 (2018) - 4 patients developed neuroregression at 2.5–3 years including ataxia in all cases due to the same (c.628G>A, p.Glu210Lys) in UBTF as previously described

- PMID: 30517966 (2018) - Single patient described with the recurrent c.628G>A variant and severe progressive neurodegeneration. He was said to have severe ataxia by age 4.

- PMID: 31931739 (2020) - Single individual reported presenting neurodegeneration with ataxia of limbs and gait as an early feature, associated with UBTF c.628G>A.

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The recurrent variant has been functionally validated in several studies and has been shown to confer a gain-of-function effect.
Created: 6 May 2021, 3:43 p.m. | Last Modified: 6 May 2021, 3:43 p.m.
Panel Version: 2.158

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672

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

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Paediatric ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants.
Sources: Expert list
Created: 13 Sep 2020, 7:55 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodegeneration, childhood-onset, with brain atrophy MIM#617672

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672
Tags
Q2_21_rating
OMIM
600673
Clinvar variants
Variants in UBTF
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

History Filter Activity

6 May 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: UBTF were set to 29300972

6 May 2021, Gel status: 2

Set mode of pathogenicity

Arina Puzriakova (Genomics England Curator)

Mode of pathogenicity for gene: UBTF was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

6 May 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

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

6 May 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: UBTF.

6 May 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 to Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672

13 Sep 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: UBTF was added gene: UBTF was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UBTF were set to 29300972 Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 Review for gene: UBTF was set to GREEN gene: UBTF was marked as current diagnostic