Genes in panel

Neurodegenerative disorders - adult onset

Gene: ITM2B

Green List (high evidence)

ITM2B (integral membrane protein 2B)
EnsemblGeneIds (GRCh38): ENSG00000136156
EnsemblGeneIds (GRCh37): ENSG00000136156
OMIM: 603904, Gene2Phenotype
ITM2B is in 4 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

two families reported - large British family with 12 affected in 3 generations; spasticity onset age 40-60 and progressive mental deterioration. No male to male transmission noted. Stop codon variant. Second Danish family, with 9 affected in 5 generations. Also no male to male transmission; cataracts before age 30 followed by cerebellar ataxia then dementia - fs that also leads to extended protein. No other variants with similar disease mechanism are reported in HMGDpro - only missense with limited evidence for pathogenicity other than in silico predictions. 2 cases - Amber?
Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.
Panel Version: 1.99

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Dementia, familial British, 176500

Publications

Mode of pathogenicity
Other - please provide details in the comments

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Green List (high evidence)

Few mutations reported.
Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.
Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Dementia, familial British, 176500

Publications

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

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Prior to GLH sign off for this panel, ITM2B was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to keep this gene Green.

It was highlighted that two fs variants and one missense rated red on HGMDpro - missense likely pathogenic using in silico tools only. Second amber rated missense in association with dementia. Only 2 cases with segregation - so it was suggested the gene should be Amber not Green. However, further feedback confirmed the Green rating as it was noted that this is rare, but there are a couple of families with a stop-loss mutation in this gene reported in one of the labs, so should remain green.
Created: 28 Nov 2019, 2:01 p.m. | Last Modified: 28 Nov 2019, 2:01 p.m.
Panel Version: 1.115
As discussed with the GMS Neurology Specialist Test Group webex call11th September 2019 : The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.
Panel Version: 1.106
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.
Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.
Panel Version: 1.101
Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.
Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.
Panel Version: 1.74
Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Created: 23 Apr 2019, 5:35 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
Phenotypes
  • Dementia, familial British, 176500
OMIM
603904
Clinvar variants
Variants in ITM2B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to ITM2B.

23 Jul 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene ITM2B were changed from to 29525180; 10391242

23 Jul 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to ITM2B.

23 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to ITM2B.

23 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to ITM2B.

25 Jan 2019, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Louise Daugherty: Comment on phenotypes: amended

18 Dec 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: ITM2B was added gene: ITM2B was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: ITM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ITM2B were set to Dementia, familial British, 176500