Optic neuropathy

Gene: AFG3L2

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 10:01 a.m. | Last Modified: 8 Mar 2022, 10:01 a.m.

Panel Version: 2.58

This gene is associated with an appropriate phenotype in OMIM. There are >3 cases supporting a gene-disease association (PMID: 29181157, 26539208, 30252181, 32600459, 32219868, 32548275). This gene will be promoted to Green gene status at the next big review of the panel and has been tagged with "for-review".

Created: 25 Aug 2020, 10:08 a.m. | Last Modified: 25 Aug 2020, 10:08 a.m.

Panel Version: 2.27

Green List (high evidence)

Another report supporting association of AFG3L2 with optic neuropathies. Caporali et al (2020) (PMID 32219868) reported several families with optic atrophy associated with AFG3L2 variants. Phenotypes ranged from isolated optic atrophy to optic atrophy associated with hearing loss, intellectual disability and ataxia, among others. Functional studies in yeast showed that variants found in this study affect AFG3L2 function (p.D407G, p.A462V, p.R465K, p.P514L, p.Q620K).

Created: 23 Jun 2020, 1:07 p.m. | Last Modified: 23 Jun 2020, 1:07 p.m.

Panel Version: 2.3

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246)

Publications

• PMID: 32219868

Green List (high evidence)

Three families reported with a recurrent missense variant associated with OA, R468C. The variant was de novo in at least one family, suggesting this is not a founder variant, but a specific residue that is functionally important in the pathogenesis of OA. Note the evidence so far is for this specific variant only, and in at least one family, the clinical presentation was with isolated OA.

Created: 16 Apr 2020, 12:15 a.m. | Last Modified: 16 Apr 2020, 12:15 a.m.

Panel Version: 2.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spastic ataxia 5, autosomal recessive (MIM#614487); Spinocerebellar ataxia 28 (MIM#610246)

Publications

• 29181157
• 26539208
• 30252181
• 30389403

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

I don't know

Some reports in literature, but possibly not enough to satisfy criteria. Additional unpublished families identified through testing (PYWM).

Created: 19 Mar 2019, 3:33 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
SPASTIC ATAXIA 5, AUTOSOMAL RECESSIVE, 614487; SPINOCEREBELLAR ATAXIA 28, 610246

Publications

• 29181157
• 26539208
• 30544562