Intellectual disability
Gene: YARS

YARS (tyrosyl-tRNA synthetase)
EnsemblGeneIds (GRCh38): ENSG00000134684
EnsemblGeneIds (GRCh37): ENSG00000134684
OMIM: 603623, Gene2Phenotype
YARS is in 5 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

As reviewed by Sarah Leigh, none of the previously reported cases presented with intellectual disability, although the family reported in PMID:30304524 had expressive language delay and the older brother reported in PMID:27633801 had mild delays.

As reviewed by Dmitrijs Rots, all 12 patients from six families identified with homozygous p.Arg367Trp variant had neurodevelopmental phenotype including intellectual disability. As all these families were identified with the same homozygous variant, the rating should remain amber.
Created: 9 Jan 2024, 10:21 a.m. | Last Modified: 9 Jan 2024, 10:21 a.m.

Panel Version: 5.380

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, OMIM:619418

Created: 9 Jan 2024, 10:21 a.m.
Last Modified: 9 Jan 2024, 10:21 a.m.
Panel version: 5.380

Dmitrijs Rots (Children's Clinical University Hospital)

12 patients with homozygous p.(Arg367Trp) have distinct NDD reported in PMID: 34536092.
Created: 16 Oct 2022, 12:27 a.m. | Last Modified: 16 Oct 2022, 12:27 a.m.

Panel Version: 3.1746

Publications

PMID: 34536092

Created: 16 Oct 2022, 12:27 a.m.
Last Modified: 16 Oct 2022, 12:27 a.m.
Panel version: 3.1746

Sarah Leigh (Genomics England Curator)

Comment on phenotypes: Monoallelic variants are associated with Charcot-Marie-Tooth disease, dominant intermediate C 608323, while biallelic variants are associated with a complex phenotype that may include intellectual disability, hearing loss and liver damage.
Created: 5 Aug 2020, 4:41 p.m. | Last Modified: 5 Aug 2020, 4:41 p.m.

Panel Version: 3.227

Comment on list classification: Biallelic variants in three families with complex clinical conditions including developmental delay. PMID 30304524 reports an extended family with microcephaly, expressive language delay, hearing loss, amongst other features. PMID 29232904 reports a proband whose phenotype included hearing loss, retnititis pigmentosa and hypotonia, but did not include intellectual disability. PMID 27633801 reports two sibblings with hypotionia, the older brother at 15 years of age has mild delays, he attends school on an individualized educational program and functions at a grade 3 level. He speaks and understands English and Polish.
Created: 6 Jul 2020, 6:25 p.m. | Last Modified: 7 Jul 2020, 2:55 p.m.

Panel Version: 3.144

The new gene for YARS is YARS1
Created: 6 Jul 2020, 5:43 p.m. | Last Modified: 6 Jul 2020, 5:43 p.m.

Panel Version: 3.143

Created: 6 Jul 2020, 5:43 p.m.
Last Modified: 7 Jul 2020, 2:55 p.m.
Panel version: 3.143

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Mono-allelic variants are associated with CMT. However, 10 individuals from three unrelated families reported with bi-allelic variants and a severe phenotype, comprising ID, nystagmus, deafness, liver dysfunction and a range of other features.
Sources: Literature
Created: 23 Apr 2020, 3:39 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; deafness; nystagmus; liver dysfunction

Publications

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

Created: 23 Apr 2020, 3:39 a.m.

Panel version: 3.31

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber

Phenotypes

Charcot-Marie-Tooth disease, dominant intermediate C 608323
Intellectual disability
deafness
nystagmus
liver dysfunction

Tags

watchlist new-gene-name

OMIM

603623

Clinvar variants

Variants in YARS

Penetrance

None

Publications

Panels with this gene