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Hearing loss

Gene: ATP2B2

Amber List (moderate evidence)

ATP2B2 (ATPase plasma membrane Ca2+ transporting 2)
EnsemblGeneIds (GRCh38): ENSG00000157087
EnsemblGeneIds (GRCh37): ENSG00000157087
OMIM: 108733, Gene2Phenotype
ATP2B2 is in 2 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on HI, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.
Created: 11 Jul 2019, 10:48 p.m. | Last Modified: 11 Jul 2019, 10:48 p.m.
Panel Version: 1.122
Comment on publications: PMID: 17234811 - Ficarella et al 2007 - A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness.
Created: 11 Jul 2019, 10:37 p.m. | Last Modified: 11 Jul 2019, 10:37 p.m.
Panel Version: 1.120
Comment on mode of inheritance: The 5 cases described in PMID: 30535804 show a monoallelic pattern of inheritance
Created: 11 Jul 2019, 10:34 p.m. | Last Modified: 11 Jul 2019, 10:34 p.m.
Panel Version: 1.118
PMID: 30535804 - Smits et al 2019 - report 5 independant cases. Whole exome sequencing in hearing impaired index cases of Dutch and Polish origins revealed five novel heterozygous (predicted to be) loss-of-function variants of ATP2B2. Two variants, c.1963G>T (p.Glu655*) and c.955delG (p.Ala319fs), occurred de novo. Three variants c.397+1G>A (p.?), c.1998C>A (p.Cys666*), and c.2329C>T (p.Arg777*), were identified in families with an autosomal dominant inheritance pattern of hearing impairment. In most cases HI was early onset, but in one individual hearing loss was reported around 55 years. Whole exome sequence (WES) data were analyzed for variants in a panel of 142 genes known to be associated with nonsyndromic hearing impairment (HI) and relatively common syndromic forms of HI. All variants affect exons, or their splice sites, that encode the ortholog of the rat PMCA2 w/a isoform. This isoform is highly abundant in stereocilia of outer hair cells (OHC) and to a lesser extent at the apical surface of inner hair cells of rats.

Although rare CDH23 variants cooccurred with ATP2B2 variants in all five index cases, they state their findings indicate that mono-allelic loss-of-function variants of ATP2B2 are the underlying cause of HI. However, variants in deep intronic regions or promoter regions were not addressed and can, therefore, not be excluded. CNVs of CDH23 can be excluded for the index cases only. They state they cannot exclude a modifying effect of the CDH23 variants on HI in the affected subjects in their study.
Created: 11 Jul 2019, 10:33 p.m. | Last Modified: 11 Jul 2019, 10:33 p.m.
Panel Version: 1.117
After review with the NHS GMS hearing specialist group on 2019-02-13 it was decided to keep this gene red.
Created: 18 Feb 2019, 10:19 a.m.

Publications

Emma Ashton (Great Ormond Street Hospital)

I don't know

reported as a modifier of AR deafness 12, one case only other is v frequent variant
Created: 17 Feb 2019, 4:35 p.m.

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#601386:{Deafness, autosomal recessive 12, modifier of}[Hearing loss, profound prelingual sensorineural; No retinitis pigmentosa]

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Expert
  • UKGTN
Phenotypes
  • {Deafness, autosomal recessive 12, modifier of} 601386
OMIM
108733
Clinvar variants
Variants in ATP2B2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

11 Jul 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: atp2b2 has been classified as Amber List (Moderate Evidence).

11 Jul 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: ATP2B2 were changed from to {Deafness, autosomal recessive 12, modifier of} 601386

11 Jul 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: ATP2B2 were set to 30535804

11 Jul 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: ATP2B2 were set to

11 Jul 2019, Gel status: 1

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: ATP2B2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ATP2B2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ATP2B2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Expert