NM_004004.6(GJB2):c.269dup (p.Val91fs) AND Autosomal recessive nonsyndromic hearing loss 1A

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 23, 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:: RCV000154347.15

Allele description [Variation Report for NM_004004.6(GJB2):c.269dup (p.Val91fs)]

NM_004004.6(GJB2):c.269dup (p.Val91fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q12.11

Genomic location:

Preferred name:

NM_004004.6(GJB2):c.269dup (p.Val91fs)

Other names:

p.Val91SerfsX11

HGVS:

NC_000013.11:g.20189313dup
NG_008358.1:g.8663dup
NM_004004.6:c.269dupMANE SELECT
NP_003995.2:p.Val91fs
LRG_1350t1:c.269dup
LRG_1350:g.8663dup
LRG_1350p1:p.Val91fs
NC_000013.10:g.20763452dup
NM_004004.5:c.269dup
NM_004004.5:c.269dupT
NM_004004.6:c.269dupTMANE SELECT

Protein change:

V91fs

Links:

dbSNP: rs730880338

NCBI 1000 Genomes Browser:

rs730880338

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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Protein Family Models
Prrt1[gene] (23)
ClinVar
CF371842 (0)
MeSH
Homo sapiens coiled-coil domain containing 71 (CCDC71), mRNA
Homo sapiens coiled-coil domain containing 71 (CCDC71), mRNA
gi|1519313943|ref|NM_022903.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000220877	Counsyl	no assertion criteria provided	Pathogenic (Mar 9, 2018)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10218527, 16380907
SCV000698240	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jun 23, 2016)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10218527, 16380907, 11102979, 23039283, 24158611 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001453340	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000220877

Counsyl

no assertion criteria provided

Pathogenic
(Mar 9, 2018)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000698240

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jun 23, 2016)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001453340

Natera, Inc.

no assertion criteria provided

Pathogenic
(Sep 16, 2020)

germline

clinical testing

Help

Summary from all submissions

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

Citations

PubMed

Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling.

Denoyelle F, Marlin S, Weil D, Moatti L, Chauvin P, Garabédian EN, Petit C.

Lancet. 1999 Apr 17;353(9161):1298-303.

PubMed [citation]

PMID:: 10218527

GJB2 mutations and degree of hearing loss: a multicenter study.

Snoeckx RL, Huygen PL, Feldmann D, Marlin S, Denoyelle F, Waligora J, Mueller-Malesinska M, Pollak A, Ploski R, Murgia A, Orzan E, Castorina P, Ambrosetti U, Nowakowska-Szyrwinska E, Bal J, Wiszniewski W, Janecke AR, Nekahm-Heis D, Seeman P, Bendova O, Kenna MA, Frangulov A, et al.

Am J Hum Genet. 2005 Dec;77(6):945-57. Epub 2005 Oct 19.

PubMed [citation]

PMID:: 16380907
PMCID:: PMC1285178

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000220877.2

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

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698240.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: The GJB2 c.269dupT (p.Val91Serfs) variant results in a premature termination codon, predicted to cause a truncated or absent GJB2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.290dupA, c.298delC, and c.313_326delAAGTTCATCAAGGG). This variant was observed in the large, broad control population, ExAC, with an allele frequency of 2/121348 (1/60674), which does not exceed the estimated maximal expected allele frequency for a pathogenic GJB2 variant of 1/40 (0.025). The variant of interest has been reported in multiple affected individuals via publications. In addition, multiple reputable databases/clinical laboratories cite the variant as "pathogenic." Therefore, the variant of interest has been classified as Pathogenic.

#	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

From Natera, Inc., SCV001453340.1

#	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: Oct 13, 2024

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