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Intellectual disability

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

2 reviews

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, 5:37 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 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.

This gene is included in gene panels for ID offered by some diagnostic laboratories (incl. Radboudumc).

As a result, AIMP2 can be considered for inclusion in this panel probably as amber.
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 14 Dec 2018, 6:17 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 17 (MIM 618006)

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
Phenotypes
  • Leukodystrophy, hypomyelinating, 17, 618006
  • neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis
OMIM
600859
Clinvar variants
Variants in AIMP2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

20 Feb 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

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

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 Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen 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 gene: AIMP2 was marked as current diagnostic