Hereditary ataxia with onset in adulthood
Gene: TMEM240
On Oxford and Sheffield panels. SCA21. 8 families reported in a french study.Created: 27 Apr 2019, 7:39 p.m.
Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Created: 27 Apr 2019, 8:55 p.m.
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.Created: 15 Apr 2019, 10:21 a.m.
Caution required here - not all of the variants reported in the original paper are absent from gnomAD as would be expected for an early onset AD gene. However, primary variant for which there is ample segregation data is fine. In addition, functional paper seems to report predominant effects in those variants appearing in gnomAD which casts doubt on usefulness of this study. Overall have two families with the original p.Pro170Leu variant, with de novo occurence in one, plus another individual with this variant in our own cohort. Just about Green List (High Evidence) on balanceCreated: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spinocerebellar ataxia 21, 607454
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Source London North GMS was added to TMEM240.
Added phenotypes Spinocerebellar ataxia 21, 607454 for gene: TMEM240
Source NHS GMS was added to TMEM240.
Source Wessex and West Midlands GLH was added to TMEM240.
Checked panel against panel constituents. Ready to promote to version 1.
Phenotypes for gene: TMEM240 were changed from Spinocerebellar ataxia 21 (#616101) to Spinocerebellar ataxia 21, 607454
gene: TMEM240 was added gene: TMEM240 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green Mode of inheritance for gene: TMEM240 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TMEM240 were set to Spinocerebellar ataxia 21 (#616101)