rs80338939

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This is a frameshift variant variant in the GJB2 gene.

Key Literature Trait Associations

Hereditary Hearing Loss

The GJB2 c.35delG (rs80338939) frameshift variant is the most common cause of autosomal recessive nonsyndromic sensorineural hearing loss (DFNB1) in European and Middle Eastern populations, accounting for the majority of pathogenic GJB2 alleles in affected individuals. Biallelic carriers (homozygous or compound heterozygous) present with congenital or prelingual profound-to-severe hearing loss. ClinVar classifies this variant as Pathogenic with expert panel review. Carrier frequencies vary substantially by ancestry: approximately 1–4% in Europeans, roughly 7% in Lithuanians, and lower in East Asians, where other GJB2 mutations predominate.

Mahdieh N et al. “Statistical study of 35delG mutation of GJB2 gene: a meta-analysis of carrier frequency.” International Journal of Audiology (2009)

Allele DEL

OR —

p —

N 23,187

Meta-analysis

multi-ancestry

Aliazami F et al. “Epidemiology, etiology, genetic variants in non- syndromic hearing loss in Iran: A systematic review and meta-analysis.” International Journal of Pediatric Otorhinolaryngology (2023)

Allele DEL

OR —

p —

N 6,995

Meta-analysis

Iranian (Middle Eastern)

Lucotte G et al. “Meta-analysis of GJB2 mutation 35delG frequencies in Europe.” Genetic Testing (2001)

Allele DEL

OR —

p —

N 4,123

Meta-analysis

European

Mikstiene V et al. “The high frequency of GJB2 gene mutation c.313_326del14 suggests its possible origin in ancestors of Lithuanian population.” Bmc Genetics (2016)

Allele DEL

OR —

p —

N 256

Candidate gene study

Lithuanian (European)

Bouzaher MH et al. “Systematic Review of Pathogenic GJB2 Variants in the Latino Population.” Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology (2020)

Allele DEL

OR —

p —

Candidate gene study

Latino

Presbycusis

A large-scale genome-wide meta-analysis (n=595,246) identified rs80338939 as a genome-wide significant locus for age-related hearing loss (presbycusis) in adults, with an odds ratio of 1.21 per allele copy (p=4×10⁻¹¹). This association is consistent with the known role of GJB2 Connexin 26 in cochlear ion homeostasis; even heterozygous carriers may have subtly compromised cochlear function that becomes clinically apparent with age-related stresses. The effect was observed in European ancestry populations across five independent cohorts.

Praveen K et al. “Population-scale analysis of common and rare genetic variation associated with hearing loss in adults.” Communications Biology (2022)

Allele DEL

OR 1.21

p 4.0e-11

N 595,246

Large GWAS

European

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Research that mentions this SNP (1)

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Identification of a novel frameshift mutation in the DFNB31/WHRN gene in a Tunisian consanguineous family with hereditary non-syndromic recessive hearing loss

AssociationN=29Abdelaziz Tlili et al.(2005)· Human Mutation

Comprehensive targeted next-generation sequencing (Mendelian exome sequencing) of 29 Turkish families with autosomal recessive nonsyndromic hearing loss identified causative variants in 21 families (72.4% detection rate). GJB2 mutations were found in 7 families, while 14 families carried mutations in 10 other known ARNSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23), with 8 novel variants identified.

Traits studied:Autosomal recessive nonsyndromic hearing loss (ARNSHL)Nonsyndromic hearing loss (NSHL)

rs80338939

Key Literature Trait Associations

Hereditary Hearing Loss

Presbycusis

Research that mentions this SNP (1)

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