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  3. ACO2
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Fetal anomalies

Gene: ACO2

Amber List (moderate evidence)
ACO2 (aconitase 2)
EnsemblGeneIds (GRCh38): ENSG00000100412
EnsemblGeneIds (GRCh37): ENSG00000100412
OMIM: 100850, Gene2Phenotype
ACO2 is in 11 panels

4 reviews

Natalie Chandler (North Thames GLH)

I don't know

This gene and phenotype were reviewed during meetings in June & July 2025. 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 & Elizabeth Scotchman (North Thames GLH), Natalie Bibb, Stephanie Allen & Sarah Graham (Central & South GLH) and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Elizabeth Wall, Sunayna Best, Soo-Mi Park & Sahar Mansour (R21 Clinical Oversight Group).
Created: 5 Sep 2025, 4:31 p.m. | Last Modified: 5 Sep 2025, 4:31 p.m.
Panel Version: 6.28
Amber in both UK & Aus panel app. Green in many other panels. Optic neuropathy. Progressive microcephaly is a feature. PMID 39891418: Microcephaly, cerebellar hypoplasia, absent cerebellar vermis, dilatation of the ventricles, thinning of the corpus callosum, CNS anomalies. Large consanguineous cohort - hom missense variant that they calssify as a VUS. Keep amber.
Created: 5 Sep 2025, 2:55 p.m. | Last Modified: 5 Sep 2025, 2:55 p.m.
Panel Version: 6.24

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile cerebellar-retinal degeneration

Publications

Created: 5 Sep 2025, 2:55 p.m.
Last Modified: 5 Sep 2025, 2:55 p.m.
Panel version: 6.28

Arina Puzriakova (Genomics England Curator)

I don't know

Amber rating has been maintained, inline with the recent review by the R21 Clinical Oversight Group.
Created: 5 Sep 2025, 4:41 p.m. | Last Modified: 5 Sep 2025, 4:41 p.m.
Panel Version: 6.29
Comment on mode of inheritance: Updated from 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' to 'BIALLELIC, autosomal or pseudoautosomal' as isolated optic atrophy caused by heterozygous variants in this gene is not relevant to the fetal panel. Extraocular features are rare in dominant cases (11%) and would also not be relevant to this panel (e.g. hearing loss, ataxia, nystagmus, metabolic dysfunction) (PMID: 34056600)
Created: 29 Aug 2025, 10:48 a.m. | Last Modified: 29 Aug 2025, 10:48 a.m.
Panel Version: 6.17
Created: 29 Aug 2025, 10:48 a.m.
Last Modified: 29 Aug 2025, 10:48 a.m.
Panel version: 6.29

Sarah Leigh (Genomics England Curator)

New paper (34056600) describing ACO2 as a cause of autosomal dominant optic atrophy - update of inheritance needed.
Tom Cullup (Great Ormond Street Hospital), 17 Feb 2022
Created: 26 May 2022, 1:26 p.m. | Last Modified: 26 May 2022, 1:26 p.m.
Panel Version: 1.863
PMID: 34056600 reports 61 cases of genetically unsolved inherited optic neuropathies who were harbouring variants in ACO2, of which 50 carried dominant variants (the remaining 11 cases were biallelic). The authors state that this is the first report of monoallelic pathogenic ACO2 variants resulting in dominant optic atrophy.
Created: 26 May 2022, 1:22 p.m. | Last Modified: 26 May 2022, 1:22 p.m.
Panel Version: 1.863

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 26 May 2022, 1:22 p.m.
Last Modified: 26 May 2022, 1:22 p.m.
Panel version: 1.863

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable for INFANTILE CEREBELLAR-RETINAL DEGENERATION
Created: 11 Dec 2018, 9:04 a.m.
Created: 11 Dec 2018, 9:04 a.m.

Panel version: 0.9

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • PAGE DD-Gene2Phenotype
Phenotypes
  • Infantile cerebellar-retinal degeneration
  • Infantile cerebellar-retinal degeneration, OMIM:614559
OMIM
100850
Clinvar variants
Variants in ACO2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

5 Sep 2025, Gel status: 2

Set Phenotypes, Set publications

Arina Puzriakova (Genomics England Curator)

Added phenotypes Infantile cerebellar-retinal degeneration for gene: ACO2 Publications for gene: ACO2 were updated from 34056600 to 34056600; 39891418

29 Aug 2025, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: ACO2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

29 Aug 2025, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: ACO2 were changed from INFANTILE CEREBELLAR-RETINAL DEGENERATION to Infantile cerebellar-retinal degeneration, OMIM:614559

26 May 2022, Gel status: 2

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

26 May 2022, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: ACO2 were set to

8 Nov 2018, Gel status: 2

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

Rebecca Foulger (Genomics England curator)

gene: ACO2 was added gene: ACO2 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: ACO2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ACO2 were set to INFANTILE CEREBELLAR-RETINAL DEGENERATION