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rs35887622

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(A;A) 0 normal hearing
(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
ReferenceGRCh38 38.1/141
Chromosome13
Position20189481
GeneGJB2
is asnp
is mentioned by
dbSNPrs35887622
dbSNP (old)rs35887622
ClinGenrs35887622
ebirs35887622
HLIrs35887622
Exacrs35887622
Varsomers35887622
Maprs35887622
PheGenIrs35887622
Biobankrs35887622
1000 genomesrs35887622
hgdprs35887622
ensemblrs35887622
gopubmedrs35887622
geneviewrs35887622
scholarrs35887622
googlers35887622
pharmgkbrs35887622
gwascentralrs35887622
openSNPrs35887622
23andMers35887622
23andMe allrs35887622
SNP Nexus

SNPshotrs35887622
SNPdbers35887622
MSV3drs35887622
GWAS Ctlgrs35887622
GMAF0.009642
Max Magnitude3

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.

hereditary non-syndromic sensorineural deafness [PMID 9139825]

OMIM121011
Desc
Variant0001
Relatedalso


ClinVar
Risk rs35887622(C;C) Rs35887622(G;G)
Alt rs35887622(C;C) Rs35887622(G;G)
Reference Rs35887622(A;A)
Significance Other
Disease Nonsyndromic hearing loss and deafness Deafness not provided Hearing impairment not specified Keratitis-Ichthyosis-Deafness Syndrome Mutilating keratoderma Nonsyndromic Hearing Loss Nonsyndromic Hearing Loss Hystrix-like ichthyosis with deafness
Variation info
Gene GJB2
CLNDBN Nonsyndromic hearing loss and deafness Deafness, autosomal recessive 1A not provided Hearing impairment not specified Keratitis-Ichthyosis-Deafness Syndrome Mutilating keratoderma Nonsyndromic Hearing Loss, Recessive Nonsyndromic Hearing Loss, Dominant Hystrix-like ichthyosis with deafness Deafness, autosomal dominant 3a
Reversed 0
HGVS NC_000013.10:g.20763620A>C; NC_000013.10:g.20763620A>G
CLNSRC HGMD OMIM Allelic Variant UniProtKB (protein)
CLNACC RCV000037811.2, RCV000018523.37, RCV000080364.4, RCV000146003.1, RCV000168670.3, RCV000211758.1, RCV000260287.1, RCV000300311.1, RCV000324780.1, RCV000355109.1, RCV000379337.1, RCV000487479.1,



[PMID 9422505] Connexin mutations and hearing loss.

[PMID 9529365OA-icon.png] Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive (DFNB1) hearing loss.

[PMID 9716127] Connexin mutations in deafness.

[PMID 10903123OA-icon.png] Autosomal recessive nonsyndromic neurosensory deafness at DFNB1 not associated with the compound-heterozygous GJB2 (connexin 26) genotype M34T/167delT.

[PMID 11134236OA-icon.png] Genetic analysis of the connexin-26 M34T variant: identification of genotype M34T/M34T segregating with mild-moderate non-syndromic sensorineural hearing loss.

[PMID 16380907OA-icon.png] 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.


GET Evidence
GJB2-M34T
aa_change Met34Thr
aa_change_short M34T
impact pathogenic
qualified_impact Moderate clinical importance, pathogenic
overall_frequency 0.00994609
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.