|(A;C)||3||Carrier of a recessive deafness mutation|
|(A;G)||3||Variant of unclear significance wrt deafness|
|(G;G)||3||Variant of unclear significance wrt deafness|
rs35887622 represents a relatively frequent variant that was originally reported to be associated with a recessive form of deafness, however more recent reports indicate that is likely to either be benign, or, perhaps, associated with mild hearing impairment, possibly of relatively late onset and progression.
A discussion of this variant can be found at OMIM 121011.0001.
[PMID 9422505] Connexin mutations and hearing loss.
[PMID 9529365] Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss.
[PMID 9716127] Connexin mutations in deafness.
[PMID 10903123] Autosomal recessive nonsyndromic neurosensory deafness at DFNB1 not associated with the compound-heterozygous GJB2 (connexin 26) genotype M34T/167delT.
[PMID 11134236] Genetic analysis of the connexin-26 M34T variant: identification of genotype M34T/M34T segregating with mild-moderate non-syndromic sensorineural hearing loss.
[PMID 16380907] GJB2 mutations and degree of hearing loss: a multicenter study.
[PMID 17935238] M34T and V37I mutations in GJB2 associated hearing impairment: evidence for pathogenicity and reduced penetrance.
[PMID 17666888] A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort.
|qualified_impact||Moderate clinical importance, pathogenic|
|summary||Several labs have reported in ClinVar that this causes deafness in a recessive manner: http://www.ncbi.nlm.nih.gov/clinvar/variation/17000/ This variant seems to be "mild", with a stronger effect when combined with a more severe variant. The variant is relatively common: according to ExAC data, 1 in 40 with European ancestry (and 1 in 25 Finnish) are carriers of this variant. Löppönen et al 2012 report that homozygotes for the variant have mild to moderate hearing impairment.|