NM_004004.6(GJB2):c.-22-12C>T AND Nonsyndromic genetic hearing loss

Germline classification:: Benign (1 submission)
Last evaluated:: Aug 31, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001257144.9

Allele description [Variation Report for NM_004004.6(GJB2):c.-22-12C>T]

NM_004004.6(GJB2):c.-22-12C>T

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.-22-12C>T

HGVS:

NC_000013.11:g.20189615G>A
NG_008358.1:g.8361C>T
NM_004004.6:c.-22-12C>TMANE SELECT
LRG_1350t1:c.-22-12C>T
LRG_1350:g.8361C>T
NC_000013.10:g.20763754G>A
NM_004004.5:c.-22-12C>T
c.-22-12C>T

Links:

dbSNP: rs9578260

NCBI 1000 Genomes Browser:

rs9578260

Molecular consequence:

NM_004004.6:c.-22-12C>T - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Nonsyndromic genetic hearing loss
Synonyms:: Nonsyndromic hearing loss and deafness; Non-syndromic genetic deafness; Nonsyndromic genetic deafness
Identifiers:: MONDO: MONDO:0019497; MedGen: C5680182; Orphanet: 87884

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001433660	INGEBI, INGEBI / CONICET	criteria provided, single submitter (ClinGen HL ACMG Specifications v1)	Benign (Aug 31, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27501294, 21392827, 30311386

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001433660

INGEBI, INGEBI / CONICET

criteria provided, single submitter

(ClinGen HL ACMG Specifications v1)

Benign
(Aug 31, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Caucasian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic Basis of Nonsyndromic Sensorineural Hearing Loss in the Sub-Saharan African Island Population of São Tomé and Príncipe: The Role of the DFNB1 Locus?

Caroça C, de Matos TM, Ribeiro D, Lourenço V, Martins T, Campelo P, Fialho G, Silva SN, Paço J, Caria H.

OMICS. 2016 Aug;20(8):449-55. doi: 10.1089/omi.2016.0067.

PubMed [citation]

PMID:: 27501294

Absence of GJB2 gene mutations, the GJB6 deletion (GJB6-D13S1830) and four common mitochondrial mutations in nonsyndromic genetic hearing loss in a South African population.

Kabahuma RI, Ouyang X, Du LL, Yan D, Hutchin T, Ramsay M, Penn C, Liu XZ.

Int J Pediatr Otorhinolaryngol. 2011 May;75(5):611-7. doi: 10.1016/j.ijporl.2011.01.029. Epub 2011 Mar 9.

PubMed [citation]

PMID:: 21392827
PMCID:: PMC4303037

See all PubMed Citations (3)

Details of each submission

From INGEBI, INGEBI / CONICET, SCV001433660.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	1	not provided	no	clinical testing	PubMed (3)

Description

Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.-22-2C>T variant in GJB2 gene is 23,4% in African population (5941/24866 alleles with 95%CI) in 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 high frequency is also supported by different publications in which controls subjects from different African populations were tested (PS4 not met, PMID: 27501294, 21392827). Benign computational prediction obtained from DANN, CADD and MaxEntScan predictors applying to BP4 rule. In summary, this variant meets criteria to be classified as benign for autosomal recessive non-syndromic hearing loss (BA1, BP4).

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

Last Updated: Oct 26, 2024

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