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Intellectual disability

Gene: FARS2

Green List (high evidence)

FARS2 (phenylalanyl-tRNA synthetase 2, mitochondrial)
EnsemblGeneIds (GRCh38): ENSG00000145982
EnsemblGeneIds (GRCh37): ENSG00000145982
OMIM: 611592, Gene2Phenotype
FARS2 is in 13 panels

3 reviews

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Although the majority of cases present with either early onset seizures or mid-childhood spasticity, in association with developmental problems, a case is reported with GDD pre-dating the seizures. In view of the evidence for the gene:disease association and a potentially relevant phenotype to an ID cohort, include as green.
Created: 19 Jul 2019, 12:10 p.m. | Last Modified: 19 Jul 2019, 12:10 p.m.
Panel Version: 0.205

Catherine Snow (Genomics England)

Comment on list classification: Expert review by Konstantinos Varvagiannis on FARS2. PMID:30869852 (Almannai et al, 2019) is a review on FARS2 deficiency. DD/ID and seizures are observed in both infantile- and later-onset forms of the disorder. The phenotype of 26 individuals (from 19 families) and 11 individuals (from 6 families) with infantile and later-onset FARS2 deficiency is summarized in table 2 of PMID:30869852.

FARS2 is in OMIM and included in the DD panel of G2P, although phenotypes are more relevant to Epilepsy panels.

There are sufficient cases of ID/DD from unrelated families to warrant a Green rating.
Created: 20 May 2019, 3:35 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 30869852 (Almannai et al, 2019) is a review on FARS2 deficiency.

DD/ID and seizures are observed in both infantile- and later-onset forms of the disorder (FARS2-related infantile-onset epileptic mitochondrial encephalopathy and FARS2-related later-onset spastic paraplegia respectively). The phenotype of 26 individuals (from 19 families) and 11 individuals (from 6 families) with infantile and later-onset FARS2 deficiency is summarized in table 2. As commented by the authors, pathogenic variants may include missense, nonsense, splice-site variants, small indels as well as larger deletions/duplications (table 1 and footnote).

The relevant OMIM entries are the following: Combined oxidative phosphorylation deficiency 14 (MIM 614946) and Spastic paraplegia 77, autosomal recessive (MIM 617046).

FARS2 is included in the DD panel of G2P, associated with Neurometabolic disorder due to FARS2 deficiency (disease confidence: confirmed).

This gene is included in gene panels for ID offered by some diagnostic laboratories.

As a result, FARS2 can be considered for inclusion in the ID panel as green (or amber)
Sources: Literature
Created: 16 Mar 2019, 7:48 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 14, 614946; Spastic paraplegia 77, autosomal recessive, 617046

Publications

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

History Filter Activity

25 Jul 2019, Gel status: 3

Added New Source, Added New Source, Set Phenotypes, Status Update

Catherine Snow (Genomics England)

Source Expert Review Green was added to FARS2. Source Expert Review was added to FARS2. Added phenotypes Spastic paraplegia 77, autosomal recessive, 617046; Combined oxidative phosphorylation deficiency 14, 614946 for gene: FARS2 Rating Changed from No List (delete) to Green List (high evidence)

16 Mar 2019, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: FARS2 was added gene: FARS2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FARS2 were set to 30869852 Phenotypes for gene: FARS2 were set to Combined oxidative phosphorylation deficiency 14, 614946; Spastic paraplegia 77, autosomal recessive, 617046 Penetrance for gene: FARS2 were set to Complete Review for gene: FARS2 was set to GREEN gene: FARS2 was marked as current diagnostic