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Genetic epilepsy syndromes

Gene: MAGI2

Green List (high evidence)

MAGI2 (membrane associated guanylate kinase, WW and PDZ domain containing 2)
EnsemblGeneIds (GRCh38): ENSG00000187391
EnsemblGeneIds (GRCh37): ENSG00000187391
OMIM: 606382, Gene2Phenotype
MAGI2 is in 8 panels

11 reviews

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Bi-allelic variants in this gene are associated with nephrotic syndrome. I cannot see seizures reported in these patients, and the Magi2-null mice have a renal phenotype.

The link to seizures as far as I can tell comes from the report of a recurrent heterozygous intragenic deletion in 2008 by Marshall et al 18565486 (as well as bigger deletions but these contain multiple genes). I am concerned there have been no reports since. This recent paper refers to the evidence re MAGI2 as contradictory and reports no increased variants in this gene in cases v controls. All pathogenic variants in ClinVar seem to relate to the nephrotic phenotype.
Created: 24 Jan 2020, 7:26 a.m. | Last Modified: 24 Jan 2020, 7:26 a.m.
Panel Version: 2.0

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy

Publications

Helen Lord (Oxford Medical Genetics Laboratories)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Rebecca Foulger (Genomics England curator)

I don't know

Comment on mode of inheritance: Updated Mode of Inheritance from 'BOTH monoallelic and biallelic' to 'BIALLELIC' based on Post-Webex review by Helen Lord (AD inheritance was based on deletions including the MAGI2 gene).
Created: 7 Sep 2019, 11:36 a.m. | Last Modified: 7 Sep 2019, 11:36 a.m.
Panel Version: 1.281
Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Comment on mode of inheritance: OMIM lists AR inheritance for 'Nephrotic syndrome, type 15' (MIM:617609). Gene2Phenotype lists 'monoallelic' inheritance for EARLY ONSET EPILEPTIC ENCEPHALOPATHY based on PMID:18565486 which examines deletions spanning MAGI2.
Created: 13 Aug 2019, 1:04 p.m. | Last Modified: 7 Sep 2019, 11:35 a.m.
Panel Version: 1.280
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)

Seizures can be part of a larger 7q11.23-q21.11 deletion and may be part of Nephrotic syndrome. AR nephrotic syndrome type 15 (NPHS15) - on pubmed. In OMIM Marshall et al 2008 - infantile spasms (IS) most severe and common form of epilepsy in early life - found 7q11.23-q21.1 interstital deletions locus for IS. The breakpoints delineate a 500kb interval within the MAG12 gene (1.4Mb in size) that is hemizygously disrupted in 15/16 participants with IS or childhood epilepsy but remains intact in 11 of 12 patients with no seizure history.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 15, 617609

Publications

Sarah Leigh (Genomics England Curator)

Comment on mode of inheritance:
OMIM reports homozygous and compound heterozygous variants in Nephrotic syndrome, type 15 617609 (PMID 27932480), whereas Gen2Phen reports hemizygous microdeletions of a 1.5 Mb region of chromosome 7q11.23 encompassing the MAGI2 gene (PMID 18565486).

Created: 7 Nov 2018, 3:29 p.m.
Comment on phenotypes: Biallelic frame shifting truncating variants associated with Nephrotic syndrome, type 15 617609
Created: 26 Sep 2018, 3:42 p.m.

Amy McTague (UCL Institute of Child Health)

Green List (high evidence)

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

Phenotypes
Infantile Spasms

Publications

  • Marshall et al (2008) Am J Hum Genet 83: 106_111,

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

Natalie Trump (NHS - Great Ormond Street Hospital)

Green List (high evidence)

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

Phenotypes
Infantile Spasms

Publications

  • Marshall et al (2008) Am J Hum Genet 83: 106_111,

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

Manju Kurian (UCL-Institute of Child Health)

Green List (high evidence)

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

Phenotypes
Infantile Spasms

Publications

  • Marshall et al (2008) Am J Hum Genet 83: 106_111,

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

Richard Scott (North Thames GMC/UCL)

Green List (high evidence)

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

Phenotypes
Infantile Spasms

Publications

  • Marshall et al (2008) Am J Hum Genet 83: 106 111,

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

Richard Scott (Genomics England Curator)

Red List (low evidence)

Insufficient evidence for diagnostic use to date - only large deletions reported
Created: 4 Feb 2016, 10:49 p.m.

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Reviews later agreed by email that the gene should be red due to lack of evidence beyond multigenic deletions. It is a possible DD gene, and so not strong evidence.
Created: 29 Jan 2016, 11:36 a.m.
The 4 reviewers decided that this gene should actually be rated red, due to lack of evidence beyond multigenic deletions.
Created: 23 Nov 2015, 5:40 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
Phenotypes
  • Nephrotic syndrome, type 15 617609
  • Infantile Spasms
Tags
cnv
OMIM
606382
Clinvar variants
Variants in MAGI2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

7 Sep 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: MAGI2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

13 Aug 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: MAGI2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to MAGI2.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to MAGI2.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Ellen McDonagh: The 4 reviewers decided that t

7 Nov 2018, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: MAGI2 were set to 18565486

7 Nov 2018, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: MAGI2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

7 Nov 2018, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: MAGI2 were changed from Infantile Spasms to Nephrotic syndrome, type 15 617609; Infantile Spasms

7 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: magi2 has been classified as Green List (High Evidence).

7 Nov 2018, Gel status: 1

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: MAGI2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal

26 Sep 2018, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: magi2 has been classified as Red List (Low Evidence).

26 Sep 2018, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: MAGI2 were changed from Infantile Spasms to Infantile Spasms

26 Sep 2018, Gel status: 1

Added Tag

Sarah Leigh (Genomics England Curator)

Tag cnv tag was added to gene: MAGI2.

31 Jul 2018, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: MAGI2 were set to 18565486

4 Apr 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

MAGI2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,UKGTN

4 Apr 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

MAGI2 was created by Sarah Leigh