Adult onset hereditary spastic paraplegia

Gene: AFG3L2

Amber List (moderate evidence)

AFG3L2 (AFG3 like matrix AAA peptidase subunit 2)
EnsemblGeneIds (GRCh38): ENSG00000141385
EnsemblGeneIds (GRCh37): ENSG00000141385
OMIM: 604581, Gene2Phenotype
AFG3L2 is in 20 panels

5 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.
Panel Version: 1.95
The following tags have been added to this gene:
Q2_21_phenotype because this gene is associated with childhood onset of ataxia, whereas this is an adult onset panel
Q2_21_MOI because biallelic and monoallelic variants are reported in ataxia associated with AFG3L2.
Created: 18 May 2021, 4:06 p.m. | Last Modified: 18 May 2021, 4:06 p.m.
Panel Version: 1.20

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Childhood onset.
Created: 20 Sep 2020, 7:48 a.m. | Last Modified: 20 Sep 2020, 7:48 a.m.
Panel Version: 1.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic ataxia 5, autosomal recessive 614487

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

Childhood onset only with a spastic ataxia phenotype. Distinct from autosomal dominant SCA28.
Created: 3 May 2019, 3:17 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Louise Daugherty (Genomics England Curator)

I don't know

Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Created: 21 May 2019, 4:14 p.m.
Review and rating submitted byJames Polke (Neurogenetics Laboratory,Institute of Neurology, London), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:50 p.m.

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

Green List (high evidence)

Victoria: early-onset spasticity resulting in significantly impaired ambulation, cerebellar ataxia, oculomotor apraxia, dystonia, and myoclonic epilepsy. Several publications, In Sheffields HSP panel
Created: 25 Apr 2019, 1:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ataxia, spastic, 5, autosomal recessive; Spastic ataxia 5, autosomal recessive; Spinocerebellar ataxia 28, autosomal dominant, 610246

History Filter Activity

19 Apr 2022, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive OMIM:614487; spastic ataxia 5 MONDO:0013776; Spinocerebellar ataxia 28 OMIM:610246; spinocerebellar ataxia type 28 MONDO:0012450 to Spastic ataxia 5, autosomal recessive, OMIM:614487

14 Mar 2022, Gel status: 2

Removed Tag, Removed Tag

Ivone Leong (Genomics England Curator)

Tag Q2_21_phenotype was removed from gene: AFG3L2. Tag Q2_21_MOI was removed from gene: AFG3L2.

14 Mar 2022, Gel status: 2

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Amber was added to AFG3L2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

18 May 2021, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive; Ataxia, spastic, 5, autosomal recessive; Spinocerebellar ataxia 28, autosomal dominant, 610246 to Spastic ataxia 5, autosomal recessive OMIM:614487; spastic ataxia 5 MONDO:0013776; Spinocerebellar ataxia 28 OMIM:610246; spinocerebellar ataxia type 28 MONDO:0012450

18 May 2021, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_21_MOI tag was added to gene: AFG3L2.

18 May 2021, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_21_phenotype tag was added to gene: AFG3L2.

13 May 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to AFG3L2.

25 Apr 2019, Gel status: 3

Added New Source, Set mode of inheritance, Set Phenotypes, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to AFG3L2. Mode of inheritance for gene AFG3L2 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Spastic ataxia 5, autosomal recessive; Ataxia, spastic, 5, autosomal recessive; Spinocerebellar ataxia 28, autosomal dominant, 610246 for gene: AFG3L2 Rating Changed from Red List (low evidence) to Green List (high evidence)

24 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to AFG3L2.

24 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: AFG3L2 was added gene: AFG3L2 was added to Hereditary spastic paraplegia - adult onset. Sources: London North GLH Mode of inheritance for gene: AFG3L2 was set to