ClinVar Genomic variation as it relates to human health
NM_004004.6(GJB2):c.-22-2A>C
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004004.6(GJB2):c.-22-2A>C
Variation ID: 375406 Accession: VCV000375406.42
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q12.11 13: 20189605 (GRCh38) [ NCBI UCSC ] 13: 20763744 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 4, 2017 Apr 15, 2024 Apr 12, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004004.6:c.-22-2A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NC_000013.11:g.20189605T>G NC_000013.10:g.20763744T>G NG_008358.1:g.8371A>C LRG_1350:g.8371A>C LRG_1350t1:c.-22-2A>C - Protein change
- Other names
- -
- Canonical SPDI
- NC_000013.11:20189604:T:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00040 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00031
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00038
1000 Genomes Project 0.00040
Trans-Omics for Precision Medicine (TOPMed) 0.00051
The Genome Aggregation Database (gnomAD) 0.00056
The Genome Aggregation Database (gnomAD), exomes 0.00061
Exome Aggregation Consortium (ExAC) 0.00068
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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GJB2 | Dosage sensitivity unlikely | No evidence available |
GRCh38 GRCh37 |
556 | - |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Mar 30, 2021 | RCV000416425.12 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Jan 25, 2024 | RCV000579320.24 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 18, 2024 | RCV000507029.12 | |
Likely pathogenic (2) |
reviewed by expert panel
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Apr 12, 2021 | RCV000710316.9 | |
Benign (1) |
criteria provided, single submitter
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Aug 23, 2017 | RCV001109960.6 | |
Benign (1) |
criteria provided, single submitter
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Aug 23, 2017 | RCV001109959.6 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 18, 2022 | RCV002481293.3 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jul 10, 2023 | RCV003323530.3 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 6, 2024 | RCV003392233.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Apr 12, 2021)
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reviewed by expert panel
Method: curation
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Nonsyndromic genetic hearing loss
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Hearing Loss Variant Curation Expert Panel
Accession: SCV000840501.7
First in ClinVar: Oct 20, 2018 Last updated: Jan 26, 2024 |
Comment:
The filtering allele frequency of the c.-22-2A>C variant in the GJB2 gene is 0.35% for Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (95% CI of 47/10344), … (more)
The filtering allele frequency of the c.-22-2A>C variant in the GJB2 gene is 0.35% for Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (95% CI of 47/10344), which meets the allele frequency threshold defined by the ClinGen Hearing Loss Expert Panel for considering strong evidence against pathogenicity for autosomal recessive hearing loss variants (BS1). However, based on the evidence outlined below, the ClinGen Hearing Loss Expert Panel believes that the evidence for the pathogenicity of this variant for nonsyndromic hearing loss outweighs its high allele frequency in population databases. Therefore, the BS1 code will not contribute to the overall classification. The c.-22-2A>C variant in the GJB2 gene has been detected in at least 9 patients with hearing loss in trans with the pathogenic c.35delG variant (PM3_Very Strong; PMID: 25401782, 24039984, 33096615; Invitae internal data, SCV000935680.2; Children’s Hospital of Philadelphia internal data, Molecular Otolaryngology and Renal Research Laboratories internal data) and one individual with the the p.Leu90Pro variant suspected in trans (PMID: 19814620). Phase was confirmed in at least 6 of these 10 observations.This variant has been reported to segregate with hearing loss in at least 2 family members (PP1; PMID: 24039984). It was also identified in the heterozygous state without a second variant in 8 individuals with hearing loss, and in the biallelic state (with c.35delG) in one individual with reportedly normal hearing (GeneDx, ARUP internal data, SCV000680741.2, SCV000603828.1). Of note, the severity of hearing loss is reported to be mild-moderate in affected probands, some with onset in the third to fourth decade, suggesting that this variant may be a hypomorphic allele. RNA analysis using patient cells demonstrated that the c.-22-2A>C variant leads to expression of a novel GJB2 transcript with a slightly longer 5' UTR but otherwise normal coding region. The alternate transcript was shown to have reduced expression, but it is not clear if the lower expression is sufficient to lead to a phenotype (PS3_Supporting; PMID: 24039984). In summary, the VCEP has used expert judgement to classify this variant as likely pathogenic for autosomal recessive hearing loss based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM3_Very Strong, PP1, PS3_Supporting, BS1. (less)
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Pathogenic
(Apr 08, 2016)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: no
Allele origin:
germline
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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Study: CSER-NextGen
Accession: SCV000494235.1 First in ClinVar: Feb 04, 2017 Last updated: Feb 04, 2017 |
Comment:
The c.-22-2A>C splice-acceptor variant in the GJB2 gene has been previously reported in 3 individuals within one generation of a single family affected with Deafness … (more)
The c.-22-2A>C splice-acceptor variant in the GJB2 gene has been previously reported in 3 individuals within one generation of a single family affected with Deafness and Hearing Loss (GandÃa et al., 2013). In all cases, this variant was observed in trans with the well-established pathogenic variant 35delG; however, these individuals experienced mild to moderate hearing loss that developed in the 3rd-4th decade of life (postlingual) (GandÃa et al., 2013). Functional splicing studies have demonstrated this variant abolishes the canonical splice-acceptor site for intron 1 of GJB2. The loss of the canonical splice-site results in a longer transcript caused by an alternative splice-acceptor site that is within intron 1(GandÃa et al., 2013). This variant is reported at low frequency in the population databases (Exome Sequencing Project = 0.058%; 1000 Genomes = 0%; and ExAC = 0.114%). Therefore, this collective evidence supports the classification of the c.-22-2A>C as a Pathogenic variant for Deafness and Hearing Loss. We have confirmed this finding in our laboratory using Sanger sequencing. (less)
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Pathogenic
(Dec 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603828.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
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Likely pathogenic
(Aug 16, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000915630.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The GJB2 c.-22-2A>C variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. The c.-22-2A>C … (more)
The GJB2 c.-22-2A>C variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. The c.-22-2A>C variant has been identified in a compound heterozygous state in four individuals with hearing loss. Three of these individuals were from a single Spanish family and exhibited mild, postlingual hearing impairment, with onset in the third to fourth decade of life (GandÃa et al. 2013). The fourth individual was of Italian origin and displayed moderate hearing impairment of unspecified onset (Stanghellini et al. 2014). In all four cases, the c.-22-2A>C variant was found in trans with a well-known pathogenic null variant, c.35delG. The Spanish pedigree also included two normal hearing heterozygous individuals, consistent with a recessive pattern of inheritance. The variant was absent from 92 normal hearing control individuals and is reported at a frequency of 0.004539 in the Ashkenazi Jewish population of the Genome Aggregation Consortium. Quantitative RT-PCR experiments indicated that the variant abolishes the canonical acceptor splice site for intron 1 of GJB2 but that a reduced amount of transcript is produced via an alternative acceptor splice site (GandÃa et al. 2013). Based on the evidence, the c.-22-2A>C allele is classified as likely pathogenic for autosomal recessive nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Benign
(Aug 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ichthyosis, hystrix-like, with hearing loss
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001267343.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(Aug 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 3A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001267344.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Likely pathogenic
(Aug 31, 2020)
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criteria provided, single submitter
Method: clinical testing
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Nonsyndromic hearing loss and deafness
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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INGEBI, INGEBI / CONICET
Accession: SCV001433672.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
Comment:
Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.-22-2A>C variant in the GJB2 gene is 0.35% … (more)
Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.-22-2A>C variant in the GJB2 gene is 0.35% (of 47/10344 alleles Ashkenazi Jewish with chromosomes with 95% CI) from Genome Aggregation Database calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/),applying to BS1 rule. The c.-22-2A>C variant has been detected in at least 4 patients with hearing loss in trans with the pathogenic c.35delG variant (PMID: 25401782, 24039984; Invitae internal data, SCV000935680.2; Laboratory of Physiology and Genetics of Hearing internal data described by ClinGen HL-EP). In addition to this, new evidence is considered since the c.-22-2A>C variant was reported in trans with p.Leu90Pro in a hearing impaired patient (PMID: 19814620, nomenclature issue checked with author: the variant called c.-24A>C in that paper is indeed c.-22-2A>C). In all those genotypes detected, patients exhibited postlingual mild-moderate hearing loss. Since this variant has a high frequency in population databases, the strength of PM3 rule was downgraded from very strong to moderate (PM3_Moderate). The c.[-22-2A>C];[35delG] genotype segregated in two affected and two unaffected members of the family (PP1_Strong; PMID: 24039984). RNA analysis showed that patients with the c.-22-2A>C variant used two alternative splice sites leading to slightly longer 5' UTR transcripts containing normal coding region but with alternated expression. This variant is suspected to be a hypomorphic allele resulting in a postlingual mild-moderate hearing loss phenotype (PS3_Supporting; PMID: 24039984). Therefore, this variant meets criteria to be classified as likely pathogenic for autosomal recessive non-syndromic hearing loss (BS1, PM3_Moderate, PP1_Strong, PS3_Supporting). (less)
Number of individuals with the variant: 1
Clinical Features:
Postlingual moderate hearing loss (present)
Family history: no
Sex: male
Ethnicity/Population group: Caucasian
Geographic origin: Argentina
Tissue: blood
Secondary finding: no
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Uncertain significance
(Mar 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: yes
Allele origin:
germline
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Neurogenetic Laboratory, Second Faculty of Medicine, Charles University
Accession: SCV001571591.1
First in ClinVar: Apr 24, 2021 Last updated: Apr 24, 2021 |
Clinical Features:
Hearing impairment (present)
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Likely pathogenic
(Feb 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Mutilating keratoderma
Autosomal dominant keratitis-ichthyosis-hearing loss syndrome Palmoplantar keratoderma-deafness syndrome Knuckle pads, deafness AND leukonychia syndrome Autosomal recessive nonsyndromic hearing loss 1A X-linked mixed hearing loss with perilymphatic gusher Autosomal dominant nonsyndromic hearing loss 3A Ichthyosis, hystrix-like, with hearing loss
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002789084.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(May 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000680741.6
First in ClinVar: Feb 13, 2018 Last updated: Jun 24, 2023 |
Comment:
Published functional studies using patient cells demonstrate the use of two alternative cryptic splice acceptor sites in lieu of the destroyed canonical splice acceptor site, … (more)
Published functional studies using patient cells demonstrate the use of two alternative cryptic splice acceptor sites in lieu of the destroyed canonical splice acceptor site, resulting in a longer 5'UTR and reduced expression of the alternate transcript; however, the coding regions remain intact and it is not clear if the lower expression is sufficient to have a clinical effect (Gandia et al., 2013); In silico analysis supports a deleterious effect on splicing; Classified as likely pathogenic by the ClinGen Hearing Loss Expert Panel (Oza et al., 2018); This variant is associated with the following publications: (PMID: 34428318, 30455902, 30311386, 29754767, 34426522, 34062854, 29016196, 19814620, 33096615, 34652575, 31053783, 31980526, DiStefano2020[paper], 24039984, 26778469, 34325055, 34308104, 36837553, 36979683) (less)
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Likely pathogenic
(Jul 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698235.4
First in ClinVar: Feb 04, 2017 Last updated: Aug 26, 2023 |
Comment:
Variant summary: GJB2 c.-22-2A>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: GJB2 c.-22-2A>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes the canonical 3' acceptor site. At least one publication reports experimental evidence that this variant leads to alternative splicing and two novel transcripts which may express some level of wild type GJB2 (Gandia_2013). However, the tissue type used in this study, saliva, may not represent the most optimal tissue type to base evidence supporting residual transcript expression in an affected tissue. A cochlear tissue, or another ear expressed tissue type may be more informative. The variant allele was found at a frequency of 0.00061 in 251058 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in GJB2 causing Autosomal Recessive Non-Syndromic Hearing Loss (0.00061 vs 0.025), allowing no conclusion about variant significance. c.-22-2A>C has been reported in the literature as a compound heterozygous genotype with c.35delG in individuals predominantly reported to have postlingual mild-moderate hearing loss (example, Gandia_2013, Burke_2016, Stanghellini_2014, Cabanillas_2018, Buonfigilio_2020). Although one conference abstract showed that there was no significant difference in allelic or genotypic frequencies between patient and control groups in an Italian subpopulation, the authors did state that the disease-causing effect of this variant when in trans with a truncating mutation cannot be excluded (Gandia_2013). Furthermore, at-least one recent study re-evaluated this variant as "Likely Pathogenic" reporting the ACMG/AMP criteria coupled with hearing-loss-gene-specific criteria of the ClinGen hearing loss expert panel (Buonfigilio_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge no direct experimental evidence evaaluating a variant specific impact on protein function and assembly have been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33096615, 26778469, 29986705, 24039984, 27057829, 35864128, 34652575, 31195736, 34062854, 25401782). Multiple clinical diagnostic laboratories and an expert panel (ClinGen Hearing Loss Variant Curation Expert Panel) have submitted clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (Pathogenic, n=2; Likely pathogenic, n=6; Benign, n=1; Likely benign, n=1, VUS, n=2 to include the expert panel). Some submitters cite overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely pathogenic for postlingual mild-moderate hearing loss. (less)
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Likely pathogenic
(May 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003834596.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000935680.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
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Likely pathogenic
(Feb 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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GJB2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004120794.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The GJB2 c.-22-2A>C variant is located in the 5' untranslated region. This variant has been reported in at least four patients with mild to moderate … (more)
The GJB2 c.-22-2A>C variant is located in the 5' untranslated region. This variant has been reported in at least four patients with mild to moderate hearing loss from two families in the compound heterozygous state with a second pathogenic variant (Gandía et al. 2013. PubMed ID: 24039984; Stanghellini et al. 2014. PubMed ID: 25401782). This variant has also been shown to disrupt the canonical splice acceptor site, although some transcripts with an intact coding region were detected (Gandía et al. 2013. PubMed ID: 24039984). This variant is reported in 0.45% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, which is higher than expected for a fully penetrant autosomal recessive pathogenic variant in this gene. This variant is classified by the ClinGen Hearing Loss Variant Curation Expert Panel as likely pathogenic for autosomal recessive hearing loss, noting the mild to moderate phenotype in some patients (https://www.ncbi.nlm.nih.gov/clinvar/variation/375406/). This variant is interpreted as likely pathogenic. (less)
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Pathogenic
(Jan 18, 2024)
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criteria provided, single submitter
Method: research
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004232558.2
First in ClinVar: Feb 04, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Oct 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004136783.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
GJB2: PM3:Very Strong, PP1:Strong, PM2:Supporting, PS3:Supporting
Number of individuals with the variant: 1
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Uncertain significance
(Apr 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132402.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Improving genetic diagnosis by disease-specific, ACMG/AMP variant interpretation guidelines for hearing loss. | Kim SY | Scientific reports | 2022 | PMID: 35864128 |
Genetic etiology of non-syndromic hearing loss in Latin America. | Lezirovitz K | Human genetics | 2022 | PMID: 34652575 |
The Cause of Hereditary Hearing Loss in GJB2 Heterozygotes-A Comprehensive Study of the GJB2/DFNB1 Region. | Safka Brozkova D | Genes | 2021 | PMID: 34062854 |
GJB2 and GJB6 Genetic Variant Curation in an Argentinean Non-Syndromic Hearing-Impaired Cohort. | Buonfiglio P | Genes | 2020 | PMID: 33096615 |
Unique Mutational Spectrum of the GJB2 Gene and its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys). | Posukh OL | Genes | 2019 | PMID: 31195736 |
Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients. | Cabanillas R | BMC medical genomics | 2018 | PMID: 29986705 |
Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing: DFNB1 or Not? | Kim SY | Medicine | 2016 | PMID: 27057829 |
Prevalence and audiological profiles of GJB2 mutations in a large collective of hearing impaired patients. | Burke WF | Hearing research | 2016 | PMID: 26778469 |
New and rare GJB2 alleles in patients with nonsyndromic sensorineural hearing impairment: a genotype/auditory phenotype correlation. | Stanghellini I | Genetic testing and molecular biomarkers | 2014 | PMID: 25401782 |
A novel splice-site mutation in the GJB2 gene causing mild postlingual hearing impairment. | Gandía M | PloS one | 2013 | PMID: 24039984 |
GJB2 mutations in patients with nonsyndromic hearing loss from Croatia. | Sansović I | Genetic testing and molecular biomarkers | 2009 | PMID: 19814620 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/09ec9aab-7e7a-4db9-b694-2ff027effd00 | - | - | - | - |
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Text-mined citations for rs201895089 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.