NM_004004.6(GJB2):c.550C>T (p.Arg184Trp) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 12, 2017
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:: RCV001089546.4

Allele description [Variation Report for NM_004004.6(GJB2):c.550C>T (p.Arg184Trp)]

NM_004004.6(GJB2):c.550C>T (p.Arg184Trp)

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.550C>T (p.Arg184Trp)

HGVS:

NC_000013.11:g.20189032G>A
NG_008358.1:g.8944C>T
NM_004004.6:c.550C>TMANE SELECT
NP_003995.2:p.Arg184Trp
LRG_1350t1:c.550C>T
LRG_1350:g.8944C>T
LRG_1350p1:p.Arg184Trp
NC_000013.10:g.20763171G>A
NM_004004.5:c.550C>T

Protein change:

R184W

Links:

dbSNP: rs998045226

NCBI 1000 Genomes Browser:

rs998045226

Molecular consequence:

NM_004004.6:c.550C>T - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001244786	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 12, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002086038	Natera, Inc.	no assertion criteria provided	Pathogenic (Aug 31, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001244786

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 12, 2017)

unknown

clinical testing

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

SCV002086038

Natera, Inc.

no assertion criteria provided

Pathogenic
(Aug 31, 2020)

germline

clinical testing

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
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV001244786.1

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

Description

The NM_004004.5(GJB2):c.550C>T missense variant identified in exon 2 of GJB2, is predicted to create a major amino acid change from an arginine to a tryptophan at amino acid position 184, NP_003995.2(GJB2):p.(Arg184Trp). The arginine at this position has high conservation (100 vertebrates, UCSC). In silico software predicts this variant to be disease causing. It is situated within the cysteine rich domain of theGJB2 protein. This variant has been observed in a population database at a frequency of 0.00001% (ExAC, GnomAD). This variant has been reported as a pathogenic variant in multiple patients with hearing loss (Deafness variation database, The Connexin-deafness homepage). Based on current information and in association with the NM_004004.5(GJB2):c.101T>C missense variant, this variant has been classified as PATHOGENIC. The presence of these two variants suggests a possible compound heterozygous mode of inheritance which is consistent with autosomal recessive deafness.

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

From Natera, Inc., SCV002086038.1

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

#	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: Feb 20, 2024

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