1. Panels
  2. Fetal anomalies
  3. EXOSC5
Genes in panel
Prev Next

Fetal anomalies

Gene: EXOSC5

Amber List (moderate evidence)
EXOSC5 (exosome component 5)
EnsemblGeneIds (GRCh38): ENSG00000077348
EnsemblGeneIds (GRCh37): ENSG00000077348
OMIM: 606492, Gene2Phenotype
EXOSC5 is in 2 panels

3 reviews

Sarah Leigh (Genomics England Curator)

I don't know

Biallelic EXOSC5 variants have been associated with Cerebellar ataxia, brain abnormalities, and cardiac conduction defects (OMIM: 619576). At least five EXOSC5 variants have been found in five unrelated families with OMIM: 619576 (PMID: 30950035, 32504085, 34089229). The most common phenotypic features were: cerebella hypophasia / atrophy (5/5 families), ataxia (4/4 families reported), hypotonia ((5/5 families) and developmental delay (4/4 families reported), all of which were apparent from infancy (supplementary table S1 in PMID:34089229).
Created: 16 Dec 2024, 2:55 p.m. | Last Modified: 16 Dec 2024, 2:55 p.m.
Panel Version: 5.5
Created: 16 Dec 2024, 2:55 p.m.
Last Modified: 16 Dec 2024, 2:55 p.m.
Panel version: 5.5

Achchuthan Shanmugasundram (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.
Panel Version: 4.36
Created: 29 Aug 2024, 8:33 p.m.
Last Modified: 29 Aug 2024, 8:33 p.m.
Panel version: 4.36

Natalie Bibb (C&S GLH)

I don't know

Amber on Ataxia and cerebellar anomalies - narrow panel. OMIM-Highly variable phenotype. PMID:32504085 (2020) - Five patients from four families with biallelic variants in EXOSC5. Clinical features included short stature (3/5), developmental delay (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved. Cerebellar ataxia was described in two sibs and one singleton - all compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 56 of EXOSC5, respectively. A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5. PMID:29302074 (2019) - Three sibs with a homozygous EXOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken. No reported prenatal presentation. Amber - more evidence of prenatal phenotype required.
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.
Panel Version: 4.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, OMIM:619576

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Amber
Phenotypes
  • Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, OMIM:619576
OMIM
606492
Clinvar variants
Variants in EXOSC5
Penetrance
None
Publications
Panels with this gene

History Filter Activity

16 Dec 2024, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: EXOSC5 were set to 32504085; 29302074; 34089229; 30950035

16 Dec 2024, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: EXOSC5 were set to 32504085; 29302074; 34089229; 30950035

16 Dec 2024, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: EXOSC5 were set to 32504085; 29302074

29 Aug 2024, Gel status: 2

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

Achchuthan Shanmugasundram (Genomics England Curator)

gene: EXOSC5 was added gene: EXOSC5 was added to Fetal anomalies. Sources: Expert Review Amber,NHS GMS Mode of inheritance for gene: EXOSC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOSC5 were set to 32504085; 29302074 Phenotypes for gene: EXOSC5 were set to Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, OMIM:619576