NM_004004.6(GJB2):c.24G>A (p.Thr8=) AND Nonsyndromic genetic hearing loss

Germline classification:: Uncertain significance (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:: RCV001257045.1

Allele description [Variation Report for NM_004004.6(GJB2):c.24G>A (p.Thr8=)]

NM_004004.6(GJB2):c.24G>A (p.Thr8=)

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.24G>A (p.Thr8=)

HGVS:

NC_000013.11:g.20189558C>T
NG_008358.1:g.8418G>A
NM_004004.6:c.24G>AMANE SELECT
NP_003995.2:p.Thr8=
LRG_1350t1:c.24G>A
LRG_1350:g.8418G>A
LRG_1350p1:p.Thr8=
NC_000013.10:g.20763697C>T
NM_004004.5:c.24G>A
NP_003995.2:p.Thr8Thr

Links:

dbSNP: rs533231493

NCBI 1000 Genomes Browser:

rs533231493

Molecular consequence:

NM_004004.6:c.24G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV001433596	INGEBI, INGEBI / CONICET	criteria provided, single submitter (ClinGen HL ACMG Specifications v1)	Uncertain significance (Aug 31, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24158611, 23668481, 30311386

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001433596

INGEBI, INGEBI / CONICET

criteria provided, single submitter

(ClinGen HL ACMG Specifications v1)

Uncertain significance
(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

Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype-phenotype analysis in moderate cases.

Dalamón V, Florencia Wernert M, Lotersztein V, Craig PO, Diamante RR, Barteik ME, Curet C, Paoli B, Mansilla E, Elgoyhen AB.

Mol Biol Rep. 2013 Dec;40(12):6945-55. doi: 10.1007/s11033-013-2814-x. Epub 2013 Oct 25.

PubMed [citation]

PMID:: 24158611

Spectrum and frequency of GJB2 mutations in a cohort of 264 Portuguese nonsyndromic sensorineural hearing loss patients.

Matos TD, Simões-Teixeira H, Caria H, Gonçalves AC, Chora J, Correia Mdo C, Moura C, Rosa H, Monteiro L, O'Neill A, Dias Ó, Andrea M, Fialho G.

Int J Audiol. 2013 Jul;52(7):466-71. doi: 10.3109/14992027.2013.783719. Epub 2013 May 13.

PubMed [citation]

PMID:: 23668481

See all PubMed Citations (3)

Details of each submission

From INGEBI, INGEBI / CONICET, SCV001433596.1

#	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.24G>A, p.(Thr8=) variant in GJB2 gene is 0,0056% (5/34592 Latino alleles with 95%CI) from Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/) which meets the criteria to apply to PM2 criteria. This variant has been identified twice in heterozygous state (PMID: 23668481, 24158611). A potential alteration of splicing was predicted by Human Splicing Finder system and Mutation Tester software applying to PP3 rule. In summary, the clinical significance of this variant is currently uncertain (PM2, PP3).

#	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: Sep 29, 2024

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