ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.-22-12C>T (rs9578260)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037804 SCV000061466 benign not specified 2017-11-27 criteria provided, single submitter clinical testing c.-22-12C>T in Intron 1 of GJB2: This variant is not expected to have clinical s ignificance because it has been identified in 24% (5729/23952) of African chromo somes by the Genome Aggregation Database (gnomAD; http://gnomad.broadinstitute.o rg; dbSNP rs9578260). ACMG/AMP Criteria applied: BA1
PreventionGenetics,PreventionGenetics RCV000037804 SCV000309910 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000272191 SCV000383062 benign Hystrix-like ichthyosis with deafness 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000327824 SCV000383063 benign Deafness, autosomal dominant 3a 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000382363 SCV000383064 benign Deafness, autosomal recessive 1A 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000433037 SCV000510980 benign not provided 2016-07-22 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000037804 SCV000603817 benign not specified 2018-07-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037804 SCV000855369 benign not specified 2017-06-21 criteria provided, single submitter clinical testing
INGEBI, INGEBI / CONICET RCV001257144 SCV001433660 benign Nonsyndromic hearing loss and deafness 2020-08-31 criteria provided, single submitter clinical testing Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.-22-2C>T variant in GJB2 gene is 23,4% in African population (5941/24866 alleles with 95%CI) in Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/). This is a high enough frequency, based on the thresholds defined by the ClinGen Hearing Loss Expert Panel, for autosomal recessive hearing loss variants to apply for BA1 rule. This high frequency is also supported by different publications in which controls subjects from different African populations were tested (PS4 not met, PMID: 27501294, 21392827). Benign computational prediction obtained from DANN, CADD and MaxEntScan predictors applying to BP4 rule. In summary, this variant meets criteria to be classified as benign for autosomal recessive non-syndromic hearing loss (BA1, BP4).

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