Adult onset neurodegenerative disorder

STR: ATXN2_CAG

Green List (high evidence)

The rating of this entity has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 4:25 p.m. | Last Modified: 26 Sep 2024, 4:25 p.m.

Panel Version: 6.5

Numerous instances of ATXN2_CAG repeat expansions have been reported in the literature associated with Amyotrophic lateral sclerosis, susceptibility to, 13 (OMIM:183090), which is an adult onset neurodegenerative disorder (PMID: 20740007;21479228;21537950;21562247;21610160).

Created: 24 Jun 2024, 3:38 p.m. | Last Modified: 24 Jun 2024, 3:39 p.m.

Panel Version: 5.6

Green List (high evidence)

Expansions in ATXN2 are a risk factor for ALS and larger expansions cause SCA2. These results have been replicated by multiple groups and a gene therapy trial to knockdown ATXN2 for ALS is ongoing. THere is growing evidence of a link between ATXN2 expression and the TDP-43 pathology that is classical of the vast majority of ALS. Thus, I strongly believe ATXN2 should have green status in the R58 panel

Created: 14 Feb 2024, 7:26 p.m. | Last Modified: 14 Feb 2024, 7:26 p.m.

Panel Version: 4.46

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
amyotrophic lateral sclerosis; spinocerebellar ataxia 2

Publications

• 20740007
• 21479228
• 21537950
• 21562247

STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.

Created: 15 Mar 2022, 11:47 a.m. | Last Modified: 15 Mar 2022, 11:47 a.m.

Panel Version: 2.267

Comment on list classification: Downgraded from Green to Amber as this STR was not listed on the recent GMS STRs document supplied by Jane Deller (NHS England) on behalf of GLHs for the GMS Neurology Test Group

Created: 8 Oct 2020, 9:27 a.m. | Last Modified: 8 Oct 2020, 9:27 a.m.

Panel Version: 2.23

Green List (high evidence)

Green rating for STR submitted on behalf of Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group. Indicated that variants are reported as part of the current diagnostic practice.

Created: 23 Jul 2019, 4:51 p.m. | Last Modified: 23 Jul 2019, 4:51 p.m.

Panel Version: 1.75

Green rating inferred from review comment of the gene by Anthony Dallosso (Bristol Genetics Laboratory) on behalf of South West GLH, needs to be confirmed during the Neurology test Group call July 2019.

Created: 9 Jul 2019, 10:18 a.m. | Last Modified: 9 Jul 2019, 10:18 a.m.

Panel Version: 1.59

Green rating for STR submitted on behalf of James Polke, also indicated that variants are reported as part of the current diagnostic practice, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 24 Apr 2019, 2:34 p.m. | Last Modified: 9 Jul 2019, 10:19 a.m.

Panel Version: 1.59

Source PanelApp panels : Hereditary ataxia v1.150, Hereditary spastic paraplegia v1.143, Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.46, Early onset dystonia v1.76, Parkinson Disease and Complex Parkinsonism v1.64.
Sources: Expert list

Created: 21 Dec 2018, 10:14 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinocerebellar ataxia 2 183090

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