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Genetic epilepsy syndromes

Gene: AIMP2

Amber List (moderate evidence)

AIMP2 (aminoacyl tRNA synthetase complex interacting multifunctional protein 2)
EnsemblGeneIds (GRCh38): ENSG00000106305
EnsemblGeneIds (GRCh37): ENSG00000106305
OMIM: 600859, Gene2Phenotype
AIMP2 is in 2 panels

5 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Kept rating as Amber based on post-Webex reviews from Helen Lord and Alison Callaway. Added 'watchlist' tag based on PMID:26795593 who report an additional case but there is uncertainty over the clinical significance of the reported variant.
Created: 9 Sep 2019, 9:29 a.m. | Last Modified: 9 Sep 2019, 9:29 a.m.
Panel Version: 1.301
Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262

Helen Lord (Oxford Medical Genetics Laboratories)

I don't know

AR HLD17. Shukla et al, 2018 (29215095) - 4 children from 2 unrelated consang families of Indian descent with a profound neurodev disorder apparent from early infancy. Early onset multifocal intractable seizures were seen. A hom nonsense variant was identified in both families Y35*. The variant was in a common region of hom in the families suggesting a founder effect. Helbig et al, 2016 (26795593) - compound het - supp data- patient 106: fs and splicing variant classed as likely pathogenic. Patient 106 also has a de novo het nonsense mutation in LRFN2 that they classify as likrly pathogenic but the overal clinicail significance is uncertain.
Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Alison Callaway (Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust)

I don't know

Additional report of an AIMP2 compound heterozygote in a patient with Epileptic Encephalopathy, Infantile Spasms in PMID 26795593 (listed in supp table S7) however this case also had a de novo change in another gene which could also explain the phenotype (but listed as uncertain).
Created: 23 Aug 2019, 10:15 a.m. | Last Modified: 23 Aug 2019, 10:15 a.m.
Panel Version: 1.256

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic Encephalopathy, Infantile Spasms

Publications

Louise Daugherty (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene currently as Amber
Created: 20 Feb 2019, 5:38 p.m.

Konstantinos Varvagiannis (Other)

I don't know

Biallelic pathogenic variants in AIMP2 cause Leukodystrophy, hypomyelinating, 17 (MIM 618006).

3 individuals from 2 unrelated consanguineous families, of Indian origin have been reported (all in PMID: 29215095).

The phenotype consisted of feeding difficulties, lack of development with intellectual disability and seizures (3/3) as well as brain MRI abnormalities (cerebral and cerebellar atrophy, hypo-intensities of the basal ganglia on T2w sequences). Severe microcephaly was observed in 2 patients for whom this information was available (birth measurements not specified).

All patients described to date were homozygous for a nonsense variant [NM_006303.3:c.105C>A or p.(Tyr35Ter)] which appears to be a founder mutation in this population.

Quantitative reverse transcription PCR demonstrated reduced mRNA levels in peripheral lymphocytes, but this decrease was not significant compared to controls (the authors presume low level of NMD).

Previous mouse models provide some - but not substantial - support.

The authors note marked similarity with the phenotype associated with AIMP1 (Leukodystrophy, hypomyelinating, 3 - MIM 260600), another auxiliary protein of the macromolecular multienzyme multi-tRNA synthetase complex. AIMP1 is listed in the current panel as green.

AIMP2 is not associated with any phenotype in G2P.

As a result, this gene can be considered for inclusion in this panel probably as amber.
Sources: Literature
Created: 14 Dec 2018, 6:19 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 17 (MIM 618006)

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Amber
Phenotypes
  • Epileptic Encephalopathy
  • Infantile Spasms
  • Leukodystrophy, hypomyelinating, 17, 618006
  • neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis
Tags
watchlist
OMIM
600859
Clinvar variants
Variants in AIMP2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to AIMP2.

17 Sep 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to AIMP2.

9 Sep 2019, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: AIMP2.

9 Sep 2019, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: AIMP2 were changed from Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis to Epileptic Encephalopathy; Infantile Spasms; Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis

9 Sep 2019, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: AIMP2 were set to 29215095

20 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: aimp2 has been classified as Amber List (Moderate Evidence).

20 Feb 2019, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: AIMP2 were changed from Leukodystrophy, hypomyelinating, 17 (MIM 618006) to Leukodystrophy, hypomyelinating, 17, 618006; neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis

14 Dec 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: AIMP2 was added gene: AIMP2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: AIMP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AIMP2 were set to 29215095 Phenotypes for gene: AIMP2 were set to Leukodystrophy, hypomyelinating, 17 (MIM 618006) Penetrance for gene: AIMP2 were set to Complete Review for gene: AIMP2 was set to AMBER