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Genetic epilepsy syndromes

Gene: PACS2

Green List (high evidence)

PACS2 (phosphofurin acidic cluster sorting protein 2)
EnsemblGeneIds (GRCh38): ENSG00000179364
EnsemblGeneIds (GRCh37): ENSG00000179364
OMIM: 610423, Gene2Phenotype
PACS2 is in 4 panels

5 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AD EIEE66 - Olson et al, 2018 - 14 unrelated children 98 months to 16 years with EIEE66 - most had onset of seizures in the first few days/weeks of life (focal motor and some had accompanying autonomic, tonic and generalised tonic-clonic seizures, seizures tend to attenuate with time). De novo het missense mutation E209K identified in all. In vitro functional expression studies showed that the PACS2 E290K variant interacted to a greater extent with the client proteins SIRT1, HDAC1 and TRPV1 compared to wt. These findings suggest that the mutation reduces the ability of the predicted autpregulatory domain to modulate the interaction beween the PACS2 and client proteins which may disturb cellular function - may be consistent with dom-neg effect.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, early infantile, 618067

Publications

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 (PMID 28867141).
Created: 17 Sep 2018, 11:26 a.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

14 unrelated patients reported with variants in this gene and EE.
Created: 18 Aug 2018, 8:50 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, early infantile, 66, MIM#618067

Publications

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, 3:53 p.m.

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

Phenotypes
Epileptic encephalopathy, early infantile, 66, 618067

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Green
Phenotypes
  • Epileptic encephalopathy, early infantile, 66, 618067
OMIM
610423
Clinvar variants
Variants in PACS2
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to PACS2.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to PACS2.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Konstantinos Varvagiannis: PMID 29656858 is a collaborati

17 Sep 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pacs2 has been classified as Green List (High Evidence).

17 Sep 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pacs2 has been classified as Green List (High Evidence).

17 Sep 2018, Gel status: 0

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PACS2 were set to 29656858; 22488736

17 Sep 2018, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

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

16 Aug 2018, Gel status: 0

Added New Source

Konstantinos Varvagiannis (Other)

PACS2 was added to Genetic Epilepsy Syndromes panel. Sources: Literature

16 Aug 2018, Gel status: 0

Created

Konstantinos Varvagiannis (Other)

PACS2 was created by Konstantinos Varvagiannis