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Hearing loss

Gene: HARS2

Amber List (moderate evidence)

HARS2 (histidyl-tRNA synthetase 2, mitochondrial)
EnsemblGeneIds (GRCh38): ENSG00000112855
EnsemblGeneIds (GRCh37): ENSG00000112855
OMIM: 600783, Gene2Phenotype
HARS2 is in 7 panels

6 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Several recent papers strengthening gene-disease association.
Created: 2 Jan 2020, 4:39 a.m. | Last Modified: 2 Jan 2020, 4:39 a.m.
Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Perrault syndrome; deafness, autosomal recessive

Publications

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

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting from red to amber as there are now 2 independent cases of variants in HARS2 in patients with Perrault syndrome.
Created: 26 Feb 2019, 4:01 p.m.
Associated provisionally with ?Perrault syndrome 2 (614926) in OMIM.

PMID: 21464306 - Pierce et al 2011 - nonconsanguineous family of mixed European ancestry with 5 affected siblings (3 females, 2 males) with Perrault syndrome. All had sensorineural hearing loss. The females also had ovarian dysgenesis. Affected individuals are compound heterozygous for HARS2 c.598C > G (p.L200V), and HARS2 c.1102G > T (p.V368L). As OMIM state functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.

PMID: 27650058 Lerat et al 2016 - Two unrelated Perrault syndrome patients from consanguineous families in Morocco had the same homozygous HARS2 mutation (c.1010A>G, p.Tyr337Cys). They presented with a similar phenotype: prelingual severe or profound deafness,secondary amenorrhea during the third decade, and no neurological sign. The originated from the same region in Morocco suggesting a founder effect.
Created: 26 Feb 2019, 3:59 p.m.

Emma Ashton (Great Ormond Street Hospital)

I don't know

Perrault syndrome, 3 DM mutations HGMD 2 families. Pierce et al 2011 family with 5 affected sibs all compound het, males have SNHL, females have ovarian dysgenesis and SNHL. Lerat et al 2016 PMID 27650058, affected patient homozygous
Created: 17 Feb 2019, 4:35 p.m.

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Demoted from green to red.
Created: 17 Feb 2016, 3:56 p.m.
Comment on list classification: Does not fit the guideline criteria for evidence.
Created: 17 Feb 2016, 3:54 p.m.

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#614926:?Perrault syndrome 2[Hearing loss, sensorineural; Immature genitalia; Ovarian dysgenesisStreak gonads; Amenorrhea, primary]

Publications

Maria Bitner-Glindzicz (UCL)

I don't know

1 family reported but good functional evidence
Created: 13 Oct 2015, 8:40 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • #614926:?Perrault syndrome 2
OMIM
600783
Clinvar variants
Variants in HARS2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

26 Feb 2019, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: HARS2 were set to PMID:12056811; 15779907; 21464306; 517579; 7755634

26 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: hars2 has been classified as Amber List (Moderate Evidence).

17 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

17 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

17 Feb 2016, Gel status: 2

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for HARS2 were set to #614926:?Perrault syndrome 2

17 Feb 2016, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for HARS2 was changed to BIALLELIC, autosomal or pseudoautosomal

17 Feb 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Feb 2016, Gel status: 3

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for HARS2 were set to PMID:12056811; 15779907; 21464306; 517579; 7755634

24 Jun 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

HARS2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert