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Severe microcephaly

Gene: COASY

Amber List (moderate evidence)

COASY (Coenzyme A synthase)
EnsemblGeneIds (GRCh38): ENSG00000068120
EnsemblGeneIds (GRCh37): ENSG00000068120
OMIM: 609855, Gene2Phenotype
COASY is in 18 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 1 Feb 2021, 6:07 p.m. | Last Modified: 1 Feb 2021, 6:07 p.m.
Panel Version: 2.98
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen (although it has a confirmed associated with Neurodegeneration with brain iron accumulation 6 OMIM:615643, PMID 24360804). At least two terminating variants have been reported in four cases of Pontocerebellar hypoplasia, type 12 OMIM:618266 in two unrelated families (PMID 30089828). Segregation and supportive functional studies were reported, together with a zebrafish morpholino knockdown, where the lack of COASY expression was rescued by addition of CoA to the water or by injection of CoA in the brain ventricle (PMID 27892483). It was proposed that the human fetuses survived gestation due to exposure to maternal CoA (PMID 30089828).
Created: 1 Feb 2021, 6:05 p.m. | Last Modified: 1 Feb 2021, 6:05 p.m.
Panel Version: 2.96
Comment on phenotypes: Variants are also associated with Neurodegeneration with brain iron accumulation 6 OMIM:615643, but this phenotype is not relevant to the Severe microcephaly panel (PMID 24360804).
Created: 1 Feb 2021, 5:43 p.m. | Last Modified: 1 Feb 2021, 5:43 p.m.
Panel Version: 2.96

Sebastian Lunke (Victorian Clinical Genetics Services)

Green List (high evidence)

6 patients from 3 families published with microcephaly. One paper (2018, 30089828) describes two families, one consanguineous with hom splice region variant c.1486-3 C>G, the other family with a compound heterozygous c.[1549_1550delAG]; [1486-3 C>G] genotype. An earlier paper (2017, 28489334) describes an additional family with two affected siblings compound het c.1495C > T; p.(R499C) and c.C641T; p(A214V) variants.
Created: 2 Sep 2020, 7:38 a.m. | Last Modified: 2 Sep 2020, 7:38 a.m.
Panel Version: 2.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Louise Daugherty (Genomics England Curator)

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62
added watchlist tag
Created: 3 Dec 2018, 11:15 a.m.
Comment on list classification: New gene. Rated Amber until more cases on gene and disease association are reported.
Created: 3 Dec 2018, 11:12 a.m.
From Dijk et al. (2018) PMID: 30089828 variants in the gene Coenzyme A (CoA) synthase (COASY) gene, an enzyme essential in CoA synthesis. A single variant was identified in 4 individuals in 2 unrelated families with PCH, prenatal onset microcephaly, and arthrogryposis. In both families, the variant c.[1549_1550delAG]; [1486-3 C>G] segregated wth the phenotype. No CoA synthase protein was detected in patient cells by immunoblot analysis and CoA synthase activity was virtually absent. Partial CoA synthase defects were previously described by Dusi et al. (2014) PMID: 24360804 as a cause of COASY Protein-Associated Neurodegeneration (CoPAN), a type of Neurodegeneration and Brain Iron Accumulation (MIM: 615643). Dijk et al. (2018) PMID: 30089828 demonstrate that near complete loss of function variants in COASY are associated with lethal PCH and arthrogryposis.
Sources: Literature
Created: 3 Dec 2018, 11:04 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis

Publications

History Filter Activity

1 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

1 Feb 2021, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: COASY were set to 30089828; 24360804

1 Feb 2021, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag for-review tag was added to gene: COASY.

1 Feb 2021, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: COASY were changed from Pontocerebellar hypoplasia, type 12 OMIM:618266 to Pontocerebellar hypoplasia, type 12 OMIM:618266

1 Feb 2021, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: COASY were changed from Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis to Pontocerebellar hypoplasia, type 12 OMIM:618266

29 Jul 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to COASY.

3 Dec 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: COASY were set to 30089828

3 Dec 2018, Gel status: 2

Added Tag

Louise Daugherty (Genomics England Curator)

Tag watchlist tag was added to gene: COASY.

3 Dec 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

3 Dec 2018, Gel status: 1

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

Louise Daugherty (Genomics England Curator)

gene: COASY was added gene: COASY was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COASY were set to 30089828 Phenotypes for gene: COASY were set to Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis Review for gene: COASY was set to AMBER