ClinVar Genomic variation as it relates to human health
NM_004004.6(GJB2):c.416G>A (p.Ser139Asn)
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.
Pathogenic(14); Likely pathogenic(4); Benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004004.6(GJB2):c.416G>A (p.Ser139Asn)
Variation ID: 44749 Accession: VCV000044749.73
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q12.11 13: 20189166 (GRCh38) [ NCBI UCSC ] 13: 20763305 (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 Nov 23, 2014 Apr 15, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_004004.6:c.416G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003995.2:p.Ser139Asn missense NC_000013.11:g.20189166C>T NC_000013.10:g.20763305C>T NG_008358.1:g.8810G>A LRG_1350:g.8810G>A LRG_1350t1:c.416G>A LRG_1350p1:p.Ser139Asn - Protein change
- S139N
- Other names
- -
- Canonical SPDI
- NC_000013.11:20189165:C:T
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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 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00029
The Genome Aggregation Database (gnomAD) 0.00047
Trans-Omics for Precision Medicine (TOPMed) 0.00036
1000 Genomes Project 0.00040
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054
Exome Aggregation Consortium (ExAC) 0.00031
1000 Genomes Project 30x 0.00047
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
Help
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 | 617 |
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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Pathogenic (1) |
criteria provided, single submitter
|
Jan 31, 2019 | RCV000037851.14 | |
Pathogenic (1) |
criteria provided, single submitter
|
Feb 8, 2013 | RCV000146022.13 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Dec 17, 2019 | RCV000289146.26 | |
Pathogenic/Likely pathogenic (10) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000255015.48 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Jun 23, 2016 | RCV000409236.11 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 18, 2017 | RCV000515309.10 | |
Pathogenic (1) |
no assertion criteria provided
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Jul 31, 2009 | RCV000678884.9 | |
Pathogenic (1) |
criteria provided, single submitter
|
- | RCV001004388.9 | |
Benign (1) |
criteria provided, single submitter
|
Apr 28, 2017 | RCV001109787.12 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 18, 2022 | RCV001844020.10 |
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
(Jan 27, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 1A
Affected status: no
Allele origin:
germline
|
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Study: CSER-NextGen
Accession: SCV000538032.2 First in ClinVar: Apr 03, 2017 Last updated: Jul 22, 2023 |
Comment:
The c.416G>A (p.Ser139Asn) missense variant in the GJB2 gene has been previously reported in at least nine individuals with autosomal recessive Nonsyndromic hearing loss and … (more)
The c.416G>A (p.Ser139Asn) missense variant in the GJB2 gene has been previously reported in at least nine individuals with autosomal recessive Nonsyndromic hearing loss and deafness. This c.416G>A variant has been observed in trans with the well-known 35delG variant in an affected individual (Marlin et al., 2001). An in vitro functional study showed this variant affects localization of the protein (Fleishman et al., 2006). The c.229C>T variant has been reported at low frequency in the c population databases (Exome Sequencing Project [ESP] = 0.0.081%, 1000 Genomes = 0.2%, and ExAC = 0.051%). Multiple in silico algorithms predict this variant to have a deleterious effect (GERP = 5.47; CADD = 24.9; PROVEAN = -2.62), and multiple reputable diagnostic laboratories report this variant as pathogenic. Therefore, this collective evidence supports the classification of the c.416G>A (p.Ser139Asn) as a recessive Likely Pathogenic variant for Nonsyndromic hearing loss and deafness. (less)
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Pathogenic
(May 09, 2017)
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criteria provided, single submitter
Method: clinical testing
|
Deafness, autosomal recessive 1A
Affected status: yes
Allele origin:
germline
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000599750.1
First in ClinVar: Sep 19, 2017 Last updated: Sep 19, 2017 |
Number of individuals with the variant: 2
|
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Pathogenic
(May 18, 2017)
|
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
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000611271.1
First in ClinVar: Nov 11, 2017 Last updated: Nov 11, 2017 |
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Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 1A
Autosomal recessive nonsyndromic hearing loss 1B
Affected status: unknown
Allele origin:
germline
|
Baylor Genetics
Accession: SCV001163360.1
First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020 |
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Pathogenic
(Feb 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603826.4
First in ClinVar: Sep 30, 2017 Last updated: Jan 08, 2022 |
Comment:
The GJB2 c.416G>A; p.Ser139Asn variant (rs76434661) is reported in the literature in multiple unrelated individuals affected with sensorineural hearing loss, and in many individuals a … (more)
The GJB2 c.416G>A; p.Ser139Asn variant (rs76434661) is reported in the literature in multiple unrelated individuals affected with sensorineural hearing loss, and in many individuals a second pathogenic variant was also identified (Dodson 2011, Gao 2016, Li 2014, Marlin 2001, Plevova 2018, Santos 2005, Snoeckx 2005, Tang 2006, Xing 2016). Additionally, the p.Ser139Asn variant is reported to co-segregate with disease in a proband and an affected sibling (Santos 2005), and functional analysis shows the variant protein fails to correctly localize to plasma membrane junctions (Fleishman 2006). This variant is classified as likely pathogenic or pathogenic by multiple laboratories in ClinVar (Variation ID: 44749). It is found in the general population with an overall allele frequency of 0.03% (89/282358 alleles) in the Genome Aggregation Database. The serine at codon 139 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.633). Based on available information, including its occurrence in multiple affected individuals, this variant is considered to be pathogenic. References: Dodson KM et al. Vestibular dysfunction in DFNB1 deafness. Am J Med Genet A. 2011 May;155A(5):993-1000. Fleishman SJ et al. The structural context of disease-causing mutations in gap junctions. J Biol Chem. 2006 Sep 29;281(39):28958-63. Gao Z et al. Application of SNPscan in Genetic Screening for Common Hearing Loss Genes. PLoS One. 2016 Oct 28;11(10):e0165650. Li Q et al. Comparative study of mutation spectrums of MT-RNR1 m.1555A>G, GJB2, and SLC26A4 between familial and sporadic patients with nonsyndromic sensorineural hearing loss in Chinese Han. Chin Med J (Engl). 2014;127(18):3233-7. Marlin S et al. Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling. Arch Otolaryngol Head Neck Surg. 2001 Aug;127(8):927-33. Plevova P et al. Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia. Medicina (Kaunas). 2018 May 4;54(2):28. Santos RL et al. Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutations. Int J Pediatr Otorhinolaryngol. 2005 Feb;69(2):165-74. Snoeckx RL et al. GJB2 mutations and degree of hearing loss: a multicenter study. Am J Hum Genet. 2005 Dec;77(6):945-57. Tang HY et al. DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls. Am J Med Genet A. 2006 Nov 15;140(22):2401-15. Xing J et al. Genetic and clinical analysis of nonsyndromic hearing impairment in pediatric and adult cases. Balkan J Med Genet. 2016 Aug 2;19(1):35-42. (less)
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Pathogenic
(Feb 18, 2022)
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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
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698255.3
First in ClinVar: Sep 19, 2017 Last updated: Mar 12, 2022 |
Comment:
Variant summary: GJB2 c.416G>A (p.Ser139Asn) results in a conservative amino acid change located in the Connexin, N-terminal domain of the encoded protein sequence. Three of … (more)
Variant summary: GJB2 c.416G>A (p.Ser139Asn) results in a conservative amino acid change located in the Connexin, N-terminal domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00029 in 251378 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in GJB2 causing Autosomal Recessive Non-Syndromic Hearing Loss (0.00029 vs 0.025), allowing no conclusion about variant significance. The variant, c.416G>A, has been reported in the literature in multiple individuals affected with Autosomal Recessive Non-Syndromic Hearing Loss in compound heterozygous state with other pathogenic or potentially pathogenic variants (Marlin_2001, Santos_2005, Snoeckx_2005, Dodson_2011, Burke_2016, Plevova_2018). Additionally, it was found to segregate with disease in two affected siblings in a family (Santos_2005). This variant has also been found in hearing loss patients whose second mutation was not identified (Wu_2002, Azaiez_2004, Dai_2009, Bazazzadegan_2012, Bonyadi_2014). These data indicate that the variant is very likely to be associated with disease. Functional studies in HeLa cells showed defective localization and coupling (Fleishman_2006). 14 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, thirteen have classified as likely pathogenic/pathogenic while one has classified as benign. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Jun 23, 2016)
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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:
unknown
|
Counsyl
Accession: SCV000487632.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
|
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Pathogenic
(Jul 13, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics Inc
Accession: SCV001143668.2
First in ClinVar: Jan 19, 2020 Last updated: Dec 31, 2022 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies in HeLa cells showed defective localization and coupling (PMID: 16864573). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. (less)
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Pathogenic
(Mar 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV003835740.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
|
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Pathogenic
(Aug 19, 2022)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002024257.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000965395.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 139 of the GJB2 protein (p.Ser139Asn). … (more)
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 139 of the GJB2 protein (p.Ser139Asn). This variant is present in population databases (rs76434661, gnomAD 0.06%). This missense change has been observed in individuals with hearing loss (PMID: 11493200, 12172394, 16380907, 17041943, 21465647, 27785406). ClinVar contains an entry for this variant (Variation ID: 44749). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJB2 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GJB2 function (PMID: 16864573). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Feb 08, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
Hearing impairment
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000193174.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
|
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Likely pathogenic
(Oct 12, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000700350.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 5
Sex: mixed
|
|
Pathogenic
(Oct 22, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000914612.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
Across a selection of the available literature, the c.416G>A (p.Ser139Asn) missense variant has been identified in 13 individuals affected with hearing loss including eight compound … (more)
Across a selection of the available literature, the c.416G>A (p.Ser139Asn) missense variant has been identified in 13 individuals affected with hearing loss including eight compound heterozygotes (including two siblings), at least five of whom carried another known pathogenic variant in trans and at least six heterozygotes (Marlin et al. 2001; Azaiez et al. 2004; Santos et al. 2005; Snoeckx et al. 2005; Tang et al. 2006; Dai et al. 2009; Dodson et al. 2011; Bonyadi et al. 2014). The p.Ser139Asn variant was absent from 761 controls and is reported at a frequency of 0.00081 in the European American population of the Exome Sequencing Project. Functional studies in HeLa cells transfected with the variant protein showed the p.Ser139Asn variant leads to mislocalization of the protein compared to wild type (Fleishman et al. 2006). Based on the collective evidence, the p.Ser139Asn variant is classified as pathogenic for autosomal recessive non-syndromic 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
(Apr 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Ichthyosis, hystrix-like, with hearing loss
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001267157.1
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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Pathogenic
(Jan 31, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Rare genetic deafness
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061513.6
First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018 |
Comment:
The p.Ser139Asn variant in GJB2 has been reported in at least 10 individuals with hearing loss, at least 7 of whom were homozygous or compound … (more)
The p.Ser139Asn variant in GJB2 has been reported in at least 10 individuals with hearing loss, at least 7 of whom were homozygous or compound heterozygous (Marlin 2001, Azaiez 2004, Santos 2005, Rikkert 2005, Tang 2006, Dai 2009, Dodson 2011, Li 2014, Bonyadi 2014, Xing 2016, Plevova 2018). Additionally, this variant segregated with disease in one affected relative from one family (Santos 2005). In vitro functional studies support that the p.Ser139Asn variant impacts protein function (Fleishman 2006). Although this variant has been identified in 0.058% (75/128800) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org), its frequency is low enough to be consistent with a recessive carrier frequency. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP criteria applied: PM3_VeryStrong, PP1, PP3, PM2_Supporting, PS3_Supporting. (less)
Number of individuals with the variant: 5
|
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Likely pathogenic
(Dec 17, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 1A
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV001193789.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 03, 2020 |
Comment:
NM_004004.5(GJB2):c.416G>A(S139N) is classified as likely pathogenic in the context of GJB2-related DFNB1 nonsyndromic hearing loss and deafness. Sources cited for classification include the following: PMID … (more)
NM_004004.5(GJB2):c.416G>A(S139N) is classified as likely pathogenic in the context of GJB2-related DFNB1 nonsyndromic hearing loss and deafness. Sources cited for classification include the following: PMID 11493200, 21465647, 25266519, 16950989, 22695344, 20234132, 17041943, 24529908, 12910486 and 12925341. Classification of NM_004004.5(GJB2):c.416G>A(S139N) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Jul 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000321728.7
First in ClinVar: Oct 09, 2016 Last updated: Apr 17, 2019 |
Comment:
Also identified in individuals with nonsyndromic hearing loss in whom no second pathogenic variant was identified (Wu et al., 2003; Azaiez et al., 2004; Bonyadi … (more)
Also identified in individuals with nonsyndromic hearing loss in whom no second pathogenic variant was identified (Wu et al., 2003; Azaiez et al., 2004; Bonyadi et al., 2014); Published functional studies suggest that the S139N variant is associated with abnormal localization of the protein (Fleishman et al., 2006); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19235794, 20668687, 20083784, 26284228, 12172394, 17666888, 19173109, 20981092, 21162657, 27785406, 27535533, 30275481, 31160754, 16864573, 32003480, 32596493, 20234132, 28483220, 30344259, 26778469, 15365987, 15656949, 16380907, 19366456, 17041943, 26444186, 25266519, 12925341, 16950989, 21465647, 22695344, 24529908, 28576516, 27018795, 29754767, 23891399, 25388846, 27153395, 27792752, 11493200, 22995991, 25087612, 12910486, 24033266) (less)
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Pathogenic
(Apr 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001245649.20
First in ClinVar: May 09, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 3
|
|
Pathogenic
(Jul 31, 2009)
|
no assertion criteria provided
Method: clinical testing
|
Hearing loss
Affected status: yes
Allele origin:
germline
|
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital
Accession: SCV000805077.1
First in ClinVar: Sep 14, 2018 Last updated: Sep 14, 2018 |
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742430.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
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Pathogenic
(Feb 12, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Autosomal recessive deafness type 1A
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002086048.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951727.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972343.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely pathogenic
(Feb 08, 2022)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 1A
Affected status: yes
Allele origin:
paternal
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Center for Molecular Medicine, Children’s Hospital of Fudan University
Accession: SCV002073945.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Sex: female
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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 |
---|---|---|---|---|
Genetic Aetiology of Nonsyndromic Hearing Loss in Moravia-Silesia. | Plevova P | Medicina (Kaunas, Lithuania) | 2018 | PMID: 30344259 |
Application of SNPscan in Genetic Screening for Common Hearing Loss Genes. | Gao Z | PloS one | 2016 | PMID: 27792752 |
Genetic and clinical analysis of nonsyndromic hearing impairment in pediatric and adult cases. | Xing J | Balkan journal of medical genetics : BJMG | 2016 | PMID: 27785406 |
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
Prevalence and audiological profiles of GJB2 mutations in a large collective of hearing impaired patients. | Burke WF | Hearing research | 2016 | PMID: 26778469 |
Bioinformatic Analysis of GJB2 Gene Missense Mutations. | Yilmaz A | Cell biochemistry and biophysics | 2015 | PMID: 25388846 |
Comparative study of mutation spectrums of MT-RNR1 m.1555A>G, GJB2, and SLC26A4 between familial and sporadic patients with nonsyndromic sensorineural hearing loss in Chinese Han. | Li Q | Chinese medical journal | 2014 | PMID: 25266519 |
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results. | Tabor HK | American journal of human genetics | 2014 | PMID: 25087612 |
Spectrum and frequency of GJB2 mutations causing deafness in the northwest of Iran. | Bonyadi MJ | International journal of pediatric otorhinolaryngology | 2014 | PMID: 24529908 |
An informatics approach to analyzing the incidentalome. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22995991 |
The spectrum of GJB2 mutations in the Iranian population with non-syndromic hearing loss--a twelve year study. | Bazazzadegan N | International journal of pediatric otorhinolaryngology | 2012 | PMID: 22695344 |
Vestibular dysfunction in DFNB1 deafness. | Dodson KM | American journal of medical genetics. Part A | 2011 | PMID: 21465647 |
Molecular epidemiological analysis of mitochondrial DNA12SrRNA A1555G, GJB2, and SLC26A4 mutations in sporadic outpatients with nonsyndromic sensorineural hearing loss in China. | Ji YB | Acta oto-laryngologica | 2011 | PMID: 21162657 |
A map of human genome variation from population-scale sequencing. | 1000 Genomes Project Consortium | Nature | 2010 | PMID: 20981092 |
GJB2 mutations and genotype-phenotype correlation in 335 patients from germany with nonsyndromic sensorineural hearing loss: evidence for additional recessive mutations not detected by current methods. | Bartsch O | Audiology & neuro-otology | 2010 | PMID: 20234132 |
GJB2 mutation spectrum in 2,063 Chinese patients with nonsyndromic hearing impairment. | Dai P | Journal of translational medicine | 2009 | PMID: 19366456 |
Hearing loss features in GJB2 biallelic mutations and GJB2/GJB6 digenic inheritance in a large Italian cohort. | Cama E | International journal of audiology | 2009 | PMID: 19173109 |
A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. | Putcha GV | Genetics in medicine : official journal of the American College of Medical Genetics | 2007 | PMID: 17666888 |
DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls. | Tang HY | American journal of medical genetics. Part A | 2006 | PMID: 17041943 |
Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: a new approach for newborn screening follow-up. | Gardner P | Pediatrics | 2006 | PMID: 16950989 |
The structural context of disease-causing mutations in gap junctions. | Fleishman SJ | The Journal of biological chemistry | 2006 | PMID: 16864573 |
GJB2 mutations and degree of hearing loss: a multicenter study. | Snoeckx RL | American journal of human genetics | 2005 | PMID: 16380907 |
Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutations. | Santos RL | International journal of pediatric otorhinolaryngology | 2005 | PMID: 15656949 |
GJB2: the spectrum of deafness-causing allele variants and their phenotype. | Azaiez H | Human mutation | 2004 | PMID: 15365987 |
Genotypic and phenotypic correlations of DFNB1-related hearing impairment in the Midwestern United States. | Lim LH | Archives of otolaryngology--head & neck surgery | 2003 | PMID: 12925341 |
Use of a multiplex PCR/sequencing strategy to detect both connexin 30 (GJB6) 342 kb deletion and connexin 26 (GJB2) mutations in cases of childhood deafness. | Wu BL | American journal of medical genetics. Part A | 2003 | PMID: 12910486 |
Effectiveness of sequencing connexin 26 (GJB2) in cases of familial or sporadic childhood deafness referred for molecular diagnostic testing. | Wu BL | Genetics in medicine : official journal of the American College of Medical Genetics | 2002 | PMID: 12172394 |
Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling. | Marlin S | Archives of otolaryngology--head & neck surgery | 2001 | PMID: 11493200 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GJB2 | - | - | - | - |
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Text-mined citations for rs76434661 ...
HelpRecord last updated Apr 20, 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.