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Hearing loss

Gene: RIPOR2

Amber List (moderate evidence)

RIPOR2 (RHO family interacting cell polarization regulator 2)
EnsemblGeneIds (GRCh38): ENSG00000111913
EnsemblGeneIds (GRCh37): ENSG00000111913
OMIM: 611410, Gene2Phenotype
RIPOR2 is in 2 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: Only two publications, describing different patterns of inheritance (AR or AD).
Created: 1 Sep 2020, 3:59 p.m. | Last Modified: 1 Sep 2020, 3:59 p.m.
Panel Version: 2.44
Comment on list classification: Recent publication described several families, but with a founder variant. Therefore currently still insufficient cases for a rating upgrade.
Created: 1 Sep 2020, 3:55 p.m. | Last Modified: 1 Sep 2020, 3:55 p.m.
Panel Version: 2.43
PMID: 32631815 (2020) - A heterozygous 12 nucleotide in-frame deletion (c.1696_1707del, p.Gln566_Lys569del) in RIPOR2 was detected in 12 families of Dutch origin with non-syndromic hearing loss.

In total, the variant was detected in 59/63 affected participants, but also in five unaffected subjects from three family. Age of onset was highly variable, from congenital to 70 years (mean age: 30.6 years) - unaffected family members who harboured the variant were aged 23, 40, 49, 50, and 51 years, respectively. The authors speculate that the four affected subjects without the variant represent phenocopies. The presence of an identical variant in 12 families of common origin, as well as haplotype analysis, indicates a founder effect.

Functional analysis of the variant showed aberrant localisation of mutant-RIPOR2 in early postnatal mouse hair cells, ex vivo; and failure to rescue the stereocilia defects of Ripor2 knockout mice, in contrast to the rescue effect observed in cells expressing wild-type RIPOR2.
Created: 1 Sep 2020, 3:51 p.m. | Last Modified: 1 Sep 2020, 3:51 p.m.
Panel Version: 2.42

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Sensorineural hearing loss

Publications

Anna de Burca (Genomics England Curator)

I don't know

PMID:24958875 used whole exome sequencing to identify a variant in RIPOR2 (formerly known as FAM65B) affecting a canonical splice site. RNA studies demonstrated skipping of exon 3 as a result of the variant. The homozygous variant segregated with hearing loss in six members of a consanguineous Turkish family with prelingual hearing loss. This remains the only case reported as pathogenic or likely pathogenic in ClinVar. PMID:27269051 and 30280293 report functional evidence for the role of RIPOR2 in the development of stereocilia, including evidence that mouse knockouts are deaf.
Created: 12 Feb 2019, 2:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sensorineural hearing loss

Publications

Louise Daugherty (Genomics England Curator)

Added new-gene-name tag. New HGNC-approved name for this gene is RIPOR2.
Created: 14 Sep 2017, 10:04 a.m.

Ellen McDonagh (Genomics England Curator)

Comment on list classification: A single variant reported in a large consanguinous Turkish family. In vitro evidence and animal model. ClinGen group have rated this strong evidence, however based on the PanelApp guidelines this gene does not reach green evidence level, and so rated amber until evidence in additional unrelated cases arises.
Created: 25 Jul 2017, 11:10 a.m.

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#616515:?Deafness, autosomal recessive 104[Deafness, sensorineural, profound]

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hearing loss, non-syndromic, autosomal recessive (Diaz-Horta (2014) Proc Natl AcadSci USA 111,9864)
  • Sensorineural hearing loss
  • OrphaNet: ORPHA90636
  • OMIM:616515
OMIM
611410
Clinvar variants
Variants in RIPOR2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

1 Sep 2020, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: RIPOR2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

1 Sep 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ripor2 has been classified as Amber List (Moderate Evidence).

5 Nov 2017, Gel status: 2

Changed Gene Name

GEL ()

FAM65B was changed to RIPOR2

5 Nov 2017, Gel status: 2

Removed Tag

GEL ()

new-gene-name was removed from FAM65B. Panel: Congenital hearing impairment (profound/severe)

25 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

25 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

25 Jul 2017, Gel status: 1

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for FAM65B were set to Hearing loss, non-syndromic, autosomal recessive (Diaz-Horta (2014) Proc Natl AcadSci USA 111,9864);Sensorineural hearing loss;OrphaNet: ORPHA90636;OMIM:616515

25 Jul 2017, Gel status: 1

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for FAM65B was changed to BIALLELIC, autosomal or pseudoautosomal

25 Jul 2017, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for FAM65B were set to 17150207; 24958875; 9055809; 9205841;24958875;27269051

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

FAM65B was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen