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Fetal anomalies

Gene: ATAD3A

Green List (high evidence)
ATAD3A (ATPase family, AAA domain containing 3A)
EnsemblGeneIds (GRCh38): ENSG00000197785
EnsemblGeneIds (GRCh37): ENSG00000197785
OMIM: 612316, Gene2Phenotype
ATAD3A is in 17 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.
Panel Version: 2.10
Comment on mode of inheritance: MOI should be updated from 'Monoallelic' to 'Both mono- and biallelic' at the next GMS panel review.

At least 7 unrelated families have now been reported with biallelic SNVs in ATAD3A, including 5 families with Harel-Yoon syndrome, MIM# 617183 (PMID: 27640307; 32607449; 33845882) and 2 families with neonatal lethal pontocerebellar hypoplasia, MIM# 618810 (PMID: 29053797; 31727539). Both of these phenotypes are pertinent to this panel.
Created: 5 Jul 2021, 3:18 p.m. | Last Modified: 5 Jul 2021, 3:18 p.m.
Panel Version: 1.682
Created: 5 Jul 2021, 3:18 p.m.
Last Modified: 5 Jul 2021, 3:18 p.m.
Panel version: 2.10

Anna de Burca (Oxford University Hospitals NHS Foundation Trust)

Green List (high evidence)

PMID: 27640307 reports a recurrent de novo variant in ATAD3A in five unrelated individuals with developmental delay and hypotonia. Some individuals had peripheral neuropathy, optic atrophy and hypertrophic cardiomyopathy. A toxic gain of function mechanism was postulated. PMID: 28327206 reports an additional case with the same de novo variant. This individual had delayed motor development and hypotonia. PMID: 27640307 also reports a biallelic missense variant in siblings of distantly related parents with motor and speech delay, hypotonia, cerebellar atrophy, ataxia, seizures, muscle weakness, cataracts and optic nerve hypoplasia. There is insufficient evidence for this association at present. Therefore, this gene should be classified green with regard to monoallelic gain of function only.
Created: 7 Jan 2019, 7:45 a.m.
PMID: 27640307 reports a recurrent de novo variant in ATAD3A in five unrelated individuals with developmental delay and hypotonia. Some individuals had peripheral neuropathy, optic atrophy and hypertrophic cardiomyopathy. A toxic gain of function mechanism was postulated. PMID: 28327206 reports an additional case with the same de novo variant. This individual had delayed motor development and hypotonia. PMID: 27640307 also reports a biallelic missense variant in siblings of distantly related parents with motor and speech delay, hypotonia, cerebellar atrophy, ataxia, seizures, muscle weakness, cataracts and optic nerve hypoplasia. There is insufficient evidence for this association at present. Therefore, this gene should be classified green with regard to monoallelic gain of function only.
Created: 7 Jan 2019, 7:45 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Harel-Yoon syndrome

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

Created: 7 Jan 2019, 7:45 a.m.

Panel version: 0.34

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 4 Apr 2019, 2:03 p.m.
Comment on mode of inheritance: Changed MOI from 'Both monoallelic and biallelic' to only monoallelic, based on Anna's review: Green rating is appropriate for monoallelic inheritance only as there is currently insufficient evidence for biallelic disorder.
Created: 7 Jan 2019, 11:33 a.m.
Comment on list classification: Updated rating from Amber to Green following review from Anna de Burca. Originally assigned an Amber rating because of different PAGE/DDG2P ratings for different disorders. Green rating is appropriate for monoallelic inheritance only, as stated in Anna's review.
Created: 7 Jan 2019, 11:32 a.m.
'watchlist' tag added to highlight different DD-G2P ratings for this gene.
Created: 8 Nov 2018, 8:56 p.m.
In the original PAGE file: rated as Confirmed for monoallelic ATAD3A disorder, and rated as Probable for biallelic ATAD3A disorder. In the original PAGE file, MOP listed as Dominant negative for monoallelic ATAD3A disorder, and listed as LOF for biallelic ATAD3A disorder.
Created: 8 Nov 2018, 4:45 p.m.
Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.161

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • PAGE DD-Gene2Phenotype
Phenotypes
  • ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy
  • Harel-Yoon syndrome, OMIM:617183
  • Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810
OMIM
612316
Clinvar variants
Variants in ATAD3A
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

30 Jan 2023, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_MOI was removed from gene: ATAD3A.

30 Jan 2023, Gel status: 3

Added New Source, Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to ATAD3A. Mode of inheritance for gene ATAD3A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

5 Jul 2021, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: ATAD3A were set to 27640307; 28327206

5 Jul 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: ATAD3A were changed from ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; Harel-Yoon syndrome, 617183 to ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; Harel-Yoon syndrome, OMIM:617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810

5 Jul 2021, Gel status: 3

Removed Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: ATAD3A. Tag Q3_21_MOI tag was added to gene: ATAD3A.

5 Jul 2021, Gel status: 3

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: ATAD3A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

7 Jan 2019, Gel status: 3

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for gene: ATAD3A was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

7 Jan 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: ATAD3A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

7 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: atad3a has been classified as Green List (High Evidence).

7 Jan 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: ATAD3A were set to

7 Jan 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: ATAD3A were changed from ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy to ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy; Harel-Yoon syndrome, 617183

8 Nov 2018, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: ATAD3A.

8 Nov 2018, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Added phenotypes ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy for gene: ATAD3A

8 Nov 2018, Gel status: 2

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

Rebecca Foulger (Genomics England curator)

gene: ATAD3A was added gene: ATAD3A was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: ATAD3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: ATAD3A were set to ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy