Intellectual disability
Gene: PACS2

PACS2 (phosphofurin acidic cluster sorting protein 2)
EnsemblGeneIds (GRCh38): ENSG00000179364
EnsemblGeneIds (GRCh37): ENSG00000179364
OMIM: 610423, Gene2Phenotype
PACS2 is in 5 panels

3 reviews

Louise Daugherty (Genomics England Curator)

Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the intellectual disability panel
Created: 26 Sep 2018, 1:40 p.m.

Created: 26 Sep 2018, 1:40 p.m.

Panel version: 2.455

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. Single de novo variant reported in at least 14 unrelated cases variants (PMID 29656858), together with previous reports of haploinsufficiency encompassing the PACS2 gene
Created: 17 Sep 2018, 12:05 p.m.

Created: 17 Sep 2018, 12:05 p.m.

Panel version: 2.442

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID 29656858 is a collaborative study reporting on 14 subjects, all with a recurrent de novo PACS2 missense variant [NM_018026.2:c.607C>T or p.(Arg203Trp)]. The phenotype is characterized by epilepsy (universal feature - neonatal or ealy infantile onset), global DD/ID (universal feature), variable cerebellar dysgenesis. A few had additional autistic features or ASD. Based on the available data, epilepsy may resolve in early childhood, so older individuals might be ascertained due to their DD/ID. There appear to be no consistent facial features. //

PMID 22488736 which is cited in the previous report, describes an individual with a minimal - 0.305 Mb - deletion encompassing PACS2 and 5 other genes. This individual presented with DD/ID and epilepsy. The authors review the cases with 14q32.3 deletions reported in the literature, although most deletions are poorly characterized or much larger and - as a result - less relevant.
Created: 16 Aug 2018, 3:48 p.m.

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

Phenotypes
Epileptic encephalopathy, early infantile, 66, 618067; Global developmental delay; Intellectual disability; Seizures; Abnormality of the cerebellum

Publications

Created: 16 Aug 2018, 3:48 p.m.

Panel version: 2.393

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green

Phenotypes

Epileptic encephalopathy, early infantile, 66, 618067
Global developmental delay
Intellectual disability
Seizures
Abnormality of the cerebellum

OMIM

610423

Clinvar variants

Variants in PACS2

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

26 Sep 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: PACS2 were changed from Epileptic encephalopathy, early infantile, 66, 618067 to Epileptic encephalopathy, early infantile, 66, 618067; Global developmental delay; Intellectual disability; Seizures; Abnormality of the cerebellum

17 Sep 2018, Gel status: 3