Submissions for variant NM_004004.6(GJB2):c.-15C>T

gnomAD frequency: 0.01589  dbSNP: rs72561725

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080361	SCV000112257	benign	not specified	2012-12-07	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080361	SCV000198170	benign	not specified	2013-06-14	criteria provided, single submitter	clinical testing	-15C>T in Exon 02 of GJB2: This variant is not expected to have clinical signifi cance because it has been identified in 5.2% (228/4406) of African American chro mosomes from a broad population by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu)
PreventionGenetics, part of Exact Sciences	RCV000080361	SCV000309909	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000297256	SCV000383057	likely benign	Autosomal recessive nonsyndromic hearing loss 1A	2018-01-12	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000266756	SCV000383059	benign	Ichthyosis, hystrix-like, with hearing loss	2018-01-12	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 Laboratory Services, Illumina	RCV000303188	SCV000383060	benign	Autosomal dominant nonsyndromic hearing loss 3A	2018-01-12	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000711346	SCV000603816	benign	not provided	2021-11-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000080361	SCV000730583	benign	not specified	2018-02-05	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.
Athena Diagnostics Inc	RCV000711346	SCV000841698	benign	not provided	2019-04-27	criteria provided, single submitter	clinical testing
INGEBI, INGEBI / CONICET	RCV001257149	SCV001433665	benign	Nonsyndromic genetic hearing loss	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.-15C>T variant in GJB2 gene is 4,86% (1271/24918 African chromosomes with 95%CI) from 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 variant is frequent (above 6%) in controls subjects from different African populations (PS4 not met, PMID: 27501294, 21392827) Benign computational verdict prediction from DANN and CADD predictors and no conservation between species (GERPscore:-5.08) applying to BP4 rule. In summary, this variant meets criteria to be classified as benign for non-syndromic hearing loss (BA1, BP4).
Invitae	RCV000711346	SCV001733243	benign	not provided	2023-09-27	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000297256	SCV001455336	benign	Autosomal recessive nonsyndromic hearing loss 1A	2020-09-16	no assertion criteria provided	clinical testing