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Hearing loss

Gene: SLC12A2

Amber List (moderate evidence)

SLC12A2 (solute carrier family 12 member 2)
EnsemblGeneIds (GRCh38): ENSG00000064651
EnsemblGeneIds (GRCh37): ENSG00000064651
OMIM: 600840, Gene2Phenotype
SLC12A2 is in 3 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - at least 10 unrelated cases (and animal models) presenting significant sensorineural hearing loss, associated with variants in SLC12A2.
Created: 8 Sep 2020, 10:39 a.m. | Last Modified: 8 Sep 2020, 10:39 a.m.
Panel Version: 2.46
- PMID: 30740830 (2019) - Homozygous 22kb deletion identified in a 5-year-old male with GDD, sensorineural hearing loss, gastrointestinal abnormalities, early postnatal respiratory distress, generalised hypotonia, and absent salivation. Neuropsychological testing demonstrated profound delays in all developmental areas, with skills ranging from 1 to 6 months. The deletion was the result of uniparental paternal isodisomy.

Functional studies using patient-derived fibroblasts showed truncated SLC12A2 transcripts and markedly reduced protein levels compared to control. Knockout mouse model recapitulated phenotypic features such as deafness, abnormal neuronal growth and migration, gastrointestinal abnormalities, and absent salivation.

- PMID: 32294086 (2020) - Homozygous SLC12A2 variant identified in one family with segregating hearing loss, as well as in three sporadic cases with de novo variants. All affected individuals presented non-syndromic congenital, severe/profound hearing loss. Some in vitro functional data showing localisation of SLC12A2 in several cells types of the cochlea and decreased expression of mutant transcripts compared to control.

- PMID: 32754646 (2020) - Compound heterozygous variants (c.1431delT and c.2006-1G>A) were identified in two sibs. The proband, an 8-year-old girl, presented a severe neurodevelopmental disorder (including severe ID), hearing impairment, gastrointestinal problems, hypotonia, and absent tear fluid, saliva, and sweat. Phenotypic overlap was noted in an affected older sister, who died at 22 days of age.

- PMID: 32658972 (2020) - Six unrelated children, all with mild-severe ID/DD, associated with de novo variants in SLC12A2. Additional clinical features included bilateral sensorineural hearing loss (2/6), abnormalities on brain MRI (2/4), and cerebral palsy (2/6). In addition, authors also identified three individuals from two unrelated families with congenital non-syndromic sensorineural hearing loss, associated with homozygous SCL12A2 variants. Some functional data in Xenopus laevis oocytes, indicating a role of SLC12A2 in neurogenesis.
Created: 8 Sep 2020, 10:36 a.m. | Last Modified: 8 Sep 2020, 10:36 a.m.
Panel Version: 2.45

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Bilateral sensorineural hearing loss; Intellectual disability; Secretory defects

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Three families reported.
Created: 3 Jun 2020, 10:45 a.m. | Last Modified: 3 Jun 2020, 10:45 a.m.
Panel Version: 2.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital, severe to profound hearing loss

Publications

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

Jun Shen (Harvard Medical School)

Red List (low evidence)

SLC12A2 is not associated with a phenotype entry in OMIM.
Created: 9 Feb 2016, 10:08 a.m.
SLC12A2 is not associated with a phenotype entry in OMIM.
Created: 7 Feb 2016, 3:45 p.m.

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert
Phenotypes
  • Bilateral sensorineural hearing loss
  • Intellectual disability
  • Secretory defects
Tags
for-review
OMIM
600840
Clinvar variants
Variants in SLC12A2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

8 Sep 2020, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: SLC12A2 were changed from to Bilateral sensorineural hearing loss; Intellectual disability; Secretory defects

8 Sep 2020, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: SLC12A2 were set to

8 Sep 2020, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: SLC12A2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

8 Sep 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: slc12a2 has been classified as Amber List (Moderate Evidence).

8 Sep 2020, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: SLC12A2.

24 Jun 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

SLC12A2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Expert