ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.-23G>T

dbSNP: rs786204734
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169581 SCV000221086 likely pathogenic Autosomal recessive nonsyndromic hearing loss 1A 2015-01-26 criteria provided, single submitter literature only
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000220459 SCV000271226 likely pathogenic Rare genetic deafness 2015-05-17 criteria provided, single submitter clinical testing The c.-23G>T variant in GJB2 has been previously reported in 2 individuals with hearing loss who were compound heterozygous with another pathogenic variant in G JB2 (Mani 2009; Tilton 2014 [conference abstract]), and was absent in 192 contro l chromosomes (Mani 2009). Data from large population studies is insufficient t o assess the frequency of this variant in the general population. This variant i s located in the last base of the exon, which is part of the 5? splice region, a nd computational tools suggest an impact to splicing. However, additional data i s needed to confirm this. In summary, although additional studies are required t o fully establish its clinical significance, the c.-23G>T variant is likely path ogenic, based on its predicted impact to splicing and its co-occurrence with a p athogenic GJB2 variant, in compound heterozygosity, in two individuals with hear ing loss.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001290620 SCV001478729 likely pathogenic Nonsyndromic genetic hearing loss 2021-01-20 criteria provided, single submitter clinical testing Variant summary: GJB2 c.-23G>T is located in the untranslated mRNA region upstream of the initiation codon. This variant is located within a splicing region and several computational tools predict a significant impact on normal splicing: Four predict that the variant abolishes a 3-prime acceptor site and abolishes or weakens a 5-prime donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 31290 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.-23G>T has been reported in the literature in compound heterozygosity with another variant in at least one individual affected with Non-Syndromic Hearing Loss (e.g. Mani_2009). These data do not allow any conclusion about variant significance. However, several other variants located within this splicing region have previously been reported as pathogenic by our laboratory (e.g. c.-22-2A>C and c.-23+1G>A) and this variant (c.-23G>T) has been reported as a "pathogenic" mutation by multiple subsequent publications (e.g. Kim_2016, Han_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories cited the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678857 SCV000805050 pathogenic Hearing loss 2017-06-02 no assertion criteria provided clinical testing
Natera, Inc. RCV000169581 SCV002086082 likely pathogenic Autosomal recessive nonsyndromic hearing loss 1A 2021-08-09 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.