Activity
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| Monogenic hearing loss v6.22 | CLRN2 |
Ida Ertmanska changed review comment from: PMID: 39446282 Ahmad et al., 2025 Consanguineous family, 2 sibs with non-syndromic profound hearing loss, homozygous for CLRN2: c.414C>A, p.Cys138*. Seq method: WES + Sanger. Variant has 1 allele reported in gnomAD (no homozygotes). Parents both heterozygous for the variant and unaffected. PMID: 33496845 (Vona et al 2021): Clrn2 mouse mutant, in which exon 2 has been deleted (Clrn2del629). Clrn2del629/del629 mice exhibit a severe-to-profound hearing loss affecting all frequencies tested. The association between CLRN2 and AR nonsyndromic genetic hearing loss was classified as Moderate in ClinGen (Hearing Loss GCEP, Sept 2025).; to: PMID: 39446282 Ahmad et al., 2025 Consanguineous family, 2 sibs with non-syndromic profound hearing loss, homozygous for CLRN2: c.414C>A, p.Cys138*. Seq method: WES + Sanger. Variant has 1 allele reported in gnomAD (no homozygotes). Parents both heterozygous for the variant and unaffected. PMID: 33496845 Vona et al 2021 Iranian family, where homozygous CLRN2: c.494C > A, p.Thr165Lys variant (expected to result in p.(Gly146Lysfs*26)) change) segregated with non-syndromic hearing loss. Clrn2 mouse mutant, in which exon 2 has been deleted (Clrn2del629). Clrn2del629/del629 mice exhibit a severe-to-profound hearing loss affecting all frequencies tested. The association between CLRN2 and AR nonsyndromic genetic hearing loss was classified as Moderate in ClinGen (Hearing Loss GCEP, Sept 2025). |
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| Monogenic hearing loss v6.22 | CLRN2 | Ida Ertmanska Classified gene: CLRN2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.22 | CLRN2 | Ida Ertmanska Added comment: Comment on list classification: There are now 2 unrelated families reported with biallelic CLRN2 variants and non-syndromic hearing loss. Mouse model supports this association, as mice homozygous for a deletion in Clrn2 exhibit a severe-to-profound hearing loss. Hence, this gene can now be promoted to Green at the next update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.22 | CLRN2 | Ida Ertmanska Gene: clrn2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.21 | CLRN2 |
Ida Ertmanska changed review comment from: PMID: 39446282 Ahmad et al., 2025 Consanguineous family, 2 sibs with non-syndromic profound hearing loss, homozygous for CLRN2: c.414C>A, p.Cys138*. Seq method: WES + Sanger. Variant has 1 allele reported in gnomAD (no homozygotes). Parents both heterozygous for the variant and unaffected. The association between CLRN2 and AR nonsyndromic genetic hearing loss was classified as Moderate in ClinGen (Hearing Loss GCEP, Sept 2025).; to: PMID: 39446282 Ahmad et al., 2025 Consanguineous family, 2 sibs with non-syndromic profound hearing loss, homozygous for CLRN2: c.414C>A, p.Cys138*. Seq method: WES + Sanger. Variant has 1 allele reported in gnomAD (no homozygotes). Parents both heterozygous for the variant and unaffected. PMID: 33496845 (Vona et al 2021): Clrn2 mouse mutant, in which exon 2 has been deleted (Clrn2del629). Clrn2del629/del629 mice exhibit a severe-to-profound hearing loss affecting all frequencies tested. The association between CLRN2 and AR nonsyndromic genetic hearing loss was classified as Moderate in ClinGen (Hearing Loss GCEP, Sept 2025). |
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| Monogenic hearing loss v6.21 | CLRN2 | Ida Ertmanska Publications for gene: CLRN2 were set to 33496845 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.20 | CLRN2 | Ida Ertmanska Tag Q2_26_promote_green tag was added to gene: CLRN2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v6.20 | CLRN2 | Ida Ertmanska reviewed gene: CLRN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39446282; Phenotypes: Deafness, autosomal recessive 117, OMIM:619174, hearing loss, autosomal recessive 117, MONDO:0030905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.168 | CLRN2 | Eleanor Williams Classified gene: CLRN2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.168 | CLRN2 | Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber as there is one extended family reported with variants in this gene, plus some supporting functional data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.168 | CLRN2 | Eleanor Williams Gene: clrn2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.167 | CLRN2 | Eleanor Williams Phenotypes for gene: CLRN2 were changed from Non-syndromic hearing loss to ?Deafness, autosomal recessive 117, OMIM:619174; deafness, autosomal recessive 117, MONDO:0030905 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.166 | CLRN2 | Eleanor Williams reviewed gene: CLRN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33496845; Phenotypes: Deafness, autosomal recessive 117, OMIM:619174, deafness, autosomal recessive 117, MONDO:0030905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.146 | CLRN2 |
Zornitza Stark gene: CLRN2 was added gene: CLRN2 was added to Hearing loss. Sources: Literature Mode of inheritance for gene: CLRN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLRN2 were set to 33496845 Phenotypes for gene: CLRN2 were set to Non-syndromic hearing loss Review for gene: CLRN2 was set to AMBER Added comment: Missense variant segregates with non-syndromic hearing loss in 3 members of a consanguineous family, two from one nuclear family and one from another. The variant was also shown to result in some transcripts being abnormally spliced, resulting in a premature stop codon. Functional studies in zebrafish and mice show the gene plays an essential role in normal organization and maintenance of the auditory hair bundles, and for hearing function. Rated Amber due to supporting functional studies in mice. Sources: Literature |
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