NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 26, 2022
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:: RCV000211776.9

Allele description [Variation Report for NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del)]

NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.355GAG[1] (p.Glu120del)

Other names:

E118del; E120delE

HGVS:

NC_000013.10:g.20763361_20763363del
NC_000013.11:g.20189222CTC[1]
NG_008358.1:g.8749GAG[1]
NM_004004.6:c.355GAG[1]MANE SELECT
NM_004004.6:c.358_360delGAG
NP_003995.2:p.Glu120del
LRG_1350t1:c.355GAG[1]
LRG_1350:g.8749GAG[1]
LRG_1350p1:p.Glu120del
NC_000013.10:g.20763361CTC[1]
NC_000013.10:g.20763361_20763363del
NC_000013.10:g.20763361_20763363delCTC
NC_000013.11:g.20189222_20189224delCTC
NM_004004.5:c.358_360delGAG
NM_004004.6:c.355GAG[1]
NM_004004.6:c.358_360delMANE SELECT
NM_004004.6:c.358_360delGAGMANE SELECT
c.358_360delGAG
c.358_360delGAG (p.Glu120del)

Protein change:

E120del; GLU118DEL

Links:

OMIM: 121011.0007; dbSNP: rs80338947

NCBI 1000 Genomes Browser:

rs80338947

Molecular consequence:

NM_004004.6:c.355GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000061503	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 26, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15666300, 12673800, 16712961, 18941476, 15967879, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061503

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 26, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

GJB2 mutations: passage through Iran.

Najmabadi H, Nishimura C, Kahrizi K, Riazalhosseini Y, Malekpour M, Daneshi A, Farhadi M, Mohseni M, Mahdieh N, Ebrahimi A, Bazazzadegan N, Naghavi A, Avenarius M, Arzhangi S, Smith RJ.

Am J Med Genet A. 2005 Mar 1;133A(2):132-7.

PubMed [citation]

PMID:: 15666300

Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating.

Tekin M, Duman T, Boğoçlu G, Incesulu A, Comak E, Ilhan I, Akar N.

Hum Mutat. 2003 May;21(5):552-3.

PubMed [citation]

PMID:: 12673800

See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061503.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The p.Glu120del variant in GJB2 has been reported in the homozygous state in more than ten probands and in the compound heterozygous state with another GJB2 pathogenic variant in more than nine probands with hearing loss (Najmabadi 2005, Tekin 2003, Hismi 2006, Marlin 2005, Mani 2008, LMM data). This variant has been identified in 17/126016 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs80338947); however, its frequency is low enough to be consistent with a recessive carrier frequency for autosomal recessive nonsyndromic hearing loss. Functional studies indicate that the channels formed by the p.Glu120del mutant protein are inactive (Mani 2008). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP criteria applied: PM3_VeryStrong, PM2, PS2_Supporting

#	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

Last Updated: Oct 20, 2024

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