NM_004004.6(GJB2):c.564_565del (p.Lys188fs) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 25, 2016
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:: RCV000602023.4

Allele description [Variation Report for NM_004004.6(GJB2):c.564_565del (p.Lys188fs)]

NM_004004.6(GJB2):c.564_565del (p.Lys188fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.564_565del (p.Lys188fs)

HGVS:

NC_000013.11:g.20189018_20189019del
NG_008358.1:g.8958_8959del
NM_004004.6:c.564_565delMANE SELECT
NP_003995.2:p.Lys188fs
LRG_1350t1:c.564_565del
LRG_1350:g.8958_8959del
LRG_1350p1:p.Lys188fs
NC_000013.10:g.20763156_20763157delTC
NC_000013.10:g.20763157_20763158del
NM_004004.5:c.564_565delGA
p.Lys188AsnfsX21

Protein change:

K188fs

Links:

dbSNP: rs770116143

NCBI 1000 Genomes Browser:

rs770116143

Molecular consequence:

NM_004004.6:c.564_565del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

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

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Streptomyces corchorusii strain DSM 40340 PRJNA299223_s006, whole genome shotgun...
Streptomyces corchorusii strain DSM 40340 PRJNA299223_s006, whole genome shotgun sequence
gi|974684023|ref|NZ_KQ948356.1||gnl NZ_LMWP01|PRJNA299223_s006

Nucleotide
603040317F1 NIH_MGC_115 Homo sapiens cDNA clone IMAGE:5181196 5', mRNA sequence
603040317F1 NIH_MGC_115 Homo sapiens cDNA clone IMAGE:5181196 5', mRNA sequence
gi|15934429|gnl|dbEST|9642156|gb|BI 9.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000712531	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Oct 25, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15365987, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000712531

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Oct 25, 2016)

germline

clinical testing

PubMed (2)
[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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

GJB2: the spectrum of deafness-causing allele variants and their phenotype.

Azaiez H, Chamberlin GP, Fischer SM, Welp CL, Prasad SD, Taggart RT, del Castillo I, Van Camp G, Smith RJ.

Hum Mutat. 2004 Oct;24(4):305-11.

PubMed [citation]

PMID:: 15365987
PMCID:: PMC10519371

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000712531.1

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

Description

The p.Lys188fs variant in GJB2 has been reported in 1 individual with hearing lo ss (Azaiez 2004). This variant has been identified in 2/10270 African chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs770116143); however, this frequency is low enough to be consistent with a r ecessive carrier frequency. This variant is predicted to cause a frameshift, whi ch alters the protein?s amino acid sequence beginning at position 188 and leads to a premature termination codon 21 amino acids downstream. In summary, this var iant is pathogenic for autosomal recessive hearing loss based on its predicted i mpact on the protein.

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

Last Updated: Dec 24, 2023

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