ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.79G>A (p.Val27Ile) (rs2274084)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037872 SCV000061534 benign not specified 2011-06-09 criteria provided, single submitter clinical testing Val27Ile in exon 2 of GJB2: This variant is benign based on its high frequency i n the general population (rs2274084) with a homozygous frequency of 12-20% in th e Asian population.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037872 SCV000112278 benign not specified 2014-11-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000037872 SCV000193183 benign not specified 2013-02-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000037872 SCV000309918 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029942 SCV000383045 benign Deafness, autosomal recessive 1A 2018-03-06 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.
GeneDx RCV000037872 SCV000513146 benign not specified 2015-12-30 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000029942 SCV000599728 benign Deafness, autosomal recessive 1A 2017-05-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000037872 SCV000603815 benign not specified 2018-07-03 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000576408 SCV000677264 benign Deafness, autosomal recessive 1A; Deafness, autosomal dominant 3a 2017-04-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001110665 SCV001268128 benign Hystrix-like ichthyosis with deafness 2018-03-06 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 RCV001110666 SCV001268129 benign Deafness, autosomal dominant 3a 2018-03-06 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.
INGEBI, INGEBI / CONICET RCV001257145 SCV001433661 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 c.79G>A variant (p.Val27Ile) in GJB2 gene is 27,2% (5547/ 19950 East Asian alleles with 95% CI), 21,7% in Latino population and 4,97% in all ethnic groups from Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which meets the allele frequency threshold defined by the ClinGen Hearing Loss Expert Panel for considering very strong evidence against pathogenicity for autosomal recessive hearing loss variants (BA1). The c.79G>A variant has been detected in high frequency in control individuals among different population (PMID: 10633133, 10983956, 15504600, 23503914, 24645897). This variant has been found in cis with pathogenic variants, applying to BP2 (PMID: 24158611). Besides, functional studies showed that p.Val27Ile mutant generated electrical conductance equal to wild type between paired Xenopus laevis oocytes. The same result was obtained when p.Val27Ile mutant was co-injected to hWtCX30, (PMID: 16300957; BS3_Supporting). In summary, this variant meets criteria to be classified as benign for autosomal recessive non-syndromic hearing loss BA1, BP2 and BS3_Supporting.
Integrated Genetics/Laboratory Corporation of America RCV000029942 SCV000052597 benign Deafness, autosomal recessive 1A 2015-03-31 no assertion criteria provided clinical testing

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