Fetal anomalies
Gene: PPP2R1A

PPP2R1A (protein phosphatase 2 scaffold subunit Aalpha)
EnsemblGeneIds (GRCh38): ENSG00000105568
EnsemblGeneIds (GRCh37): ENSG00000105568
OMIM: 605983, Gene2Phenotype
PPP2R1A is in 7 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Intellectual disability with variable other features, including CC abnormalities and microcephaly/macrocephaly.

Likely dominant negative. For some variants, binding assays using HEK293T cells transfected with either WT or mutant constructs demonstrated decreased binding to B subunit families or C subunit with corresponding decrease in PP2A activity by affecting the trimeric holoenzyme (hypothesized by authors) ((PMIDs: 26168268, 33106617).

Established functional domains/hotspots: Heat repeats (approx. aa 160-235) (Decipher).
Created: 24 Jun 2021, 11:14 a.m. | Last Modified: 24 Jun 2021, 11:14 a.m.

Panel Version: 0.3889

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605

Created: 24 Jun 2021, 11:14 a.m.
Last Modified: 24 Jun 2021, 11:14 a.m.
Panel version: Imported from Intellectual disability syndromic and non-syndromic panel version 0.3889

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

Likely dominant negative. For some variants, binding assays using HEK293T cells transfected with either WT or mutant constructs demonstrated decreased binding to B subunit families or C subunit with corresponding decrease in PP2A activity by affecting the trimeric holoenzyme (hypothesized by authors) ((PMIDs: 26168268, 33106617).

11/29 patients were macrocephalic, conversely 7/29 patients were microcephalic. All variants were in the same region and all were missense.
Sources: Literature
Created: 23 Jun 2021, 11:55 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mental retardation, autosomal dominant 36 MIM#616362

Publications

PMID: 33106617
26168268

Mode of pathogenicity
Other

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

Created: 23 Jun 2021, 11:55 p.m.

Panel version: Imported from Microcephaly panel version 1.26

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Genomics England PanelApp
Literature
Genetic Health Queensland

Phenotypes

Mental retardation, autosomal dominant 36, MIM#616362
Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605

OMIM

605983

Clinvar variants

Variants in PPP2R1A

Penetrance

None

Publications

Mode of Pathogenicity

Other

Panels with this gene