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Genetic epilepsy syndromes

Gene: RANBP2

Amber List (moderate evidence)

RANBP2 (RAN binding protein 2)
EnsemblGeneIds (GRCh38): ENSG00000153201
EnsemblGeneIds (GRCh37): ENSG00000153201
OMIM: 601181, Gene2Phenotype
RANBP2 is in 7 panels

5 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

p.Thr585Met gnomAD frequency (1/245874) and seen in 9 of 15 families suspected of having familial or recurrent acute necrotizing encephalopathy. Potential risk factor. AD susceptibility to acute infection induced encephalopathy 3 (IIAE3). Molecular genetics on OMIM - Neilson et al 2009 - suggest that mutations in RANBP2 gene predispose to acute necrotising encephalopathy following febrile illness - but by themselves are insufficient to make the phenotype fully penetrant and additional genetic and environmental factors are required. In addition 4 more affected famiies did not carry RANBP2 mutations
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
{Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033

Publications

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: Amber.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Demoted RANBP2 from Green to Amber following review by Zornitza Stark and agreement from Helen Brittain (Genomics England clinical team). Recent papers report patients with symptoms (including seizures) after a viral illness (PMID:30796099, PMID:28336122, PMID:25128471). However, listed as a susceptibility locus in OMIM, and papers report incomplete penetrance: variant present in asymptomatic maternal grandmother in PMID:30796099 and in the father in PMID:28336122. Therefore further information (e.g. on penetrance) is required for a clear gene:disease association.
Created: 25 Jul 2019, 3:28 p.m. | Last Modified: 25 Jul 2019, 3:29 p.m.
Panel Version: 1.181

Zornitza Stark (Australian Genomics)

Red List (low evidence)

We consider this a susceptibility gene, rather than a true monogenic condition, and as such would only analyse when specifically indicated based on presenting features and report only variants where increased risk is clearly established.
Created: 20 Aug 2018, 10:15 a.m.

Andrea Haworth (ACGS, Congenica)

The condition associated with RANBP2 is reported in gene reviews and other publications as monoallelic with incomplete penetrance
https://www.ncbi.nlm.nih.gov/books/NBK258641/
PMID: 25522933
PMID: 19118815
Created: 30 Sep 2017, 8:57 a.m.

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Comment on publications: publications suggested by Andrea Haworth (ACGS, Congenica) as evidence for autosomal incomplete penetrance
Created: 9 Oct 2017, 10:42 a.m.
Comment on "Treatable" tag: Early diagnosis could allow potentially beneficial measures, such as ensuring up-to-date immunization status (eg, against influenza), though full protection against all inciting agents would not be possible
Created: 20 Mar 2017, 11:22 a.m.
Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.
Created: 20 Mar 2017, 11:21 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Amber
  • Expert Review
Phenotypes
  • {Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033
OMIM
601181
Clinvar variants
Variants in RANBP2
Penetrance
None
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to RANBP2.

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to RANBP2.

25 Jul 2019, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: ranbp2 has been classified as Amber List (Moderate Evidence).

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Sarah Leigh: Inclusion of this as a green g

8 Nov 2018, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: RANBP2 were changed from {Encephalopathy, acute, infection-induced, 3, susceptibility to} to {Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033

4 Apr 2018, Gel status: 4

Added New Source

Sarah Leigh (Genomics England Curator)

RANBP2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review,Expert Review Green

4 Apr 2018, Gel status: 4

Created

Sarah Leigh (Genomics England Curator)

RANBP2 was created by Sarah Leigh