Genes in panel
STRs in panel
Prev Next
Regions in panel
Prev Next

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 8 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)

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review
Created: 29 Jun 2020, 12:38 p.m. | Last Modified: 29 Jun 2020, 12:38 p.m.
Panel Version: 2.23
6 new cases, so now 8 independent cases, which is sufficient to rate green.

New cases:

PMID: 31827252 - Demain et al 2019 - 3 unrelated families each with compound heterozygous variants in HARS2 in affected members. All 3 families share the c.1439G>A p.(Arg480His) (NM_012208.3) variant along with other likely pathogenic variants.

PMID: 31449985 - Karstensen et al 2019 - three novel families, compound heterozygous for missense variants in HARS2 and early onset, rapidly progressive hearing impairment in the five affected individuals. Premature ovarian insufficiency was also seen in some individuals.
Created: 28 Jan 2020, 11:56 a.m. | Last Modified: 28 Jan 2020, 11:56 a.m.
Panel Version: 2.4
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
Tags
for-review
OMIM
600783
Clinvar variants
Variants in HARS2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

29 Jun 2020, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: HARS2.

29 Jun 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

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