GJB2 V27I - GET-Evidence

Curation:
Currentness:

GJB2 V27I

(GJB2 Val27Ile)


Short summary

Probable non-pathogenic; other variants in gene associated with hearing loss.
A few controversial mutations of uncertain or evolving clinical significance are included in this prototype.
Examples include V27I, M34T, V37I, and E114G in the GJB2 gene and IVS2-2AG in the SLC26A5 gene.
This variant is also observed both in Case and Control in the study of hearing loss.

Variant evidence
Computational 1

Other variants in GJB2 associated with hearing loss

See Rickard S et al. 2001 (11494963).

Functional -
Case/Control 2

In Chinese population, variant allele associated with lack of hearing loss (controls) with p = 0.04;
homozygotes have reduced hearing loss with p = 0.02 in chi-squared test. Haplotypes with T at both rs2274084 and rs2274083 associated with lack of hearing loss with Fisher’s exact test p = 0.005
Study of Altai with hearing loss found no significant association of V27I

See Cheng HB et al. 2009 (19719946), Posukh O et al. 2005 (15790391).

Familial -
 
Clinical importance
Severity

See Posukh O et al. 2005 (15790391), Cheng HB et al. 2009 (19719946).

Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr13:20763642: 0.3% (29/10758) in EVS
  • T @ chr13:19661641: 7.8% (10/128) in GET-Evidence
  • Frequency shown in summary reports: 0.3% (29/10758)

Publications
 

Rickard S, Kelsell DP, Sirimana T, Rajput K, MacArdle B, Bitner-Glindzicz M. Recurrent mutations in the deafness gene GJB2 (connexin 26) in British Asian families. J Med Genet. 2001 Aug;38(8):530-3. PubMed PMID: 11494963; PubMed Central PMCID: PMC1734923.

 

Posukh O, Pallares-Ruiz N, Tadinova V, Osipova L, Claustres M, Roux AF. First molecular screening of deafness in the Altai Republic population. BMC Med Genet. 2005 Mar 24;6:12. PubMed PMID: 15790391; PubMed Central PMCID: PMC1079841.

 

Cheng HB, Chen ZB, Wei QJ, Lu YJ, Xing GQ, Cao X. Single nucleotide polymorphisms and haplotypes analysis of DFNB1 locus in Chinese sporadic hearing impairment population. Chin Med J (Engl). 2009 Jul 5;122(13):1549-53. PubMed PMID: 19719946.

 

Genomes
 

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het T @ chr13:20763642

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
het T @ chr13:20763642

 

GS18526 - var-GS18526-1100-36-ASM
het T @ chr13:19661642

 

GS18537 - var-GS18537-1100-36-ASM
hom T @ chr13:19661642

 

GS18558 - var-GS18558-1100-36-ASM
hom T @ chr13:19661642

 

GS18942 - var-GS18942-1100-36-ASM
het T @ chr13:19661642

 

GS18947 - var-GS18947-1100-36-ASM
het T @ chr13:19661642

 

GS19648 - var-GS19648-1100-36-ASM
het T @ chr13:19661642

 

GS19670 - var-GS19670-1100-36-ASM
het T @ chr13:19661642

 

GS19735 - var-GS19735-1100-36-ASM
het T @ chr13:19661642

 

Other external references
 

    dbSNP
  • rs2274084
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the GJB2 gene
    Nonsyndromic Hearing Loss and Deafness, Autosomal Recessive
    Nonsyndromic Hearing Loss and Deafness, Autosomal Dominant
    DFNA 3 Nonsyndromic Hearing Loss and Deafness
    DFNB 1 Nonsyndromic Hearing Loss and Deafness
    GJB2-Related DFNA 3 Nonsyndromic Hearing Loss and Deafness
    GJB2-Related DFNB 1 Nonsyndromic Hearing Loss and Deafness
    Ichthyosis, Hystrix-like, with Deafness
    Keratitis-Ichthyosis-Deafness Syndrome, Autosomal Dominant
    Vohwinkel Syndrome
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GJB2
    PolyPhen-2
  • Score: 0.981 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = –4
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in