NM_004004.6(GJB2):c.-22-6T>C AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 30, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001109963.13

Allele description [Variation Report for NM_004004.6(GJB2):c.-22-6T>C]

NM_004004.6(GJB2):c.-22-6T>C

Gene:

GJB2:gap junction protein beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.-22-6T>C

HGVS:

NC_000013.11:g.20189609A>G
NG_008358.1:g.8367T>C
NM_004004.6:c.-22-6T>CMANE SELECT
LRG_1350t1:c.-22-6T>C
LRG_1350:g.8367T>C
NC_000013.10:g.20763748A>G
NM_004004.5:c.-22-6T>C

Links:

dbSNP: rs141962118

NCBI 1000 Genomes Browser:

rs141962118

Molecular consequence:

NM_004004.6:c.-22-6T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 1A (DFNB1A)
Synonyms:: Deafness nonsyndromic, Connexin 26 linked; Deafness, autosomal recessive 1A; DFNB 1 Nonsyndromic Hearing Loss and Deafness; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009076; MedGen: C2673759; Orphanet: 90636; OMIM: 220290

Recent activity

Clear Turn Off Turn On

Homo sapiens chromosome 14 open reading frame 1, mRNA (cDNA clone MGC:1219 IMAGE...
Homo sapiens chromosome 14 open reading frame 1, mRNA (cDNA clone MGC:1219 IMAGE:3347242), complete cds
gi|33990698|gb|BC002444.2|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001267347	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17041943, 25401782 Citation Link,
SCV001571590	Neurogenetic Laboratory, Second Faculty of Medicine, Charles University	criteria provided, single submitter (ClinGen HL ACMG Specifications v1)	Uncertain significance (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001267347

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001571590

Neurogenetic Laboratory, Second Faculty of Medicine, Charles University

criteria provided, single submitter

(ClinGen HL ACMG Specifications v1)

Uncertain significance
(Mar 30, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, Fang P, Ward PA, Schmitt E, Darilek S, Manolidis S, Oghalai JS, Roa BB, Alford RL.

Am J Med Genet A. 2006 Nov 15;140(22):2401-15. Erratum in: Am J Med Genet A. 2008 Nov 15;146A(22):2979..

PubMed [citation]

PMID:: 17041943
PMCID:: PMC3623690

New and rare GJB2 alleles in patients with nonsyndromic sensorineural hearing impairment: a genotype/auditory phenotype correlation.

Stanghellini I, Genovese E, Palma S, Ravani A, Falcinelli C, Guarnaccia MC, Percesepe A.

Genet Test Mol Biomarkers. 2014 Dec;18(12):839-44. doi: 10.1089/gtmb.2014.0185.

PubMed [citation]

PMID:: 25401782

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001267347.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neurogenetic Laboratory, Second Faculty of Medicine, Charles University, SCV001571590.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

ClinVar

Relating variation to medicine