NM_004004.6(GJB2):c.269T>C (p.Leu90Pro) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 10, 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:: RCV000211772.13

Allele description [Variation Report for NM_004004.6(GJB2):c.269T>C (p.Leu90Pro)]

NM_004004.6(GJB2):c.269T>C (p.Leu90Pro)

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.269T>C (p.Leu90Pro)

HGVS:

NC_000013.11:g.20189313A>G
NG_008358.1:g.8663T>C
NM_004004.6:c.269T>CMANE SELECT
NP_003995.2:p.Leu90Pro
NP_003995.2:p.Leu90Pro
LRG_1350t1:c.269T>C
LRG_1350:g.8663T>C
LRG_1350p1:p.Leu90Pro
NC_000013.10:g.20763452A>G
NM_004004.5:c.269T>C
P29033:p.Leu90Pro
c.269T>C
c.269T>C (p.Leu90Pro)
p.LEU90PRO

Protein change:

L90P; LEU90PRO

Links:

UniProtKB: P29033#VAR_015937; OMIM: 121011.0016; dbSNP: rs80338945

NCBI 1000 Genomes Browser:

rs80338945

Molecular consequence:

NM_004004.6:c.269T>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Observations:

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
SCV000061493	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Aug 10, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 14985372, 22281373, 22037723, 19941053, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061493

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Aug 10, 2017)

germline

clinical testing

PubMed (5)
[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	38	33	not provided	not provided	not provided	clinical testing

Citations

PubMed

A genotype-phenotype correlation for GJB2 (connexin 26) deafness.

Cryns K, Orzan E, Murgia A, Huygen PL, Moreno F, del Castillo I, Chamberlin GP, Azaiez H, Prasad S, Cucci RA, Leonardi E, Snoeckx RL, Govaerts PJ, Van de Heyning PH, Van de Heyning CM, Smith RJ, Van Camp G.

J Med Genet. 2004 Mar;41(3):147-54.

PubMed [citation]

PMID:: 14985372
PMCID:: PMC1735685

Prevalence of DFNB1 mutations in Slovak patients with non-syndromic hearing loss.

Minárik G, Tretinárová D, Szemes T, Kádasi L.

Int J Pediatr Otorhinolaryngol. 2012 Mar;76(3):400-3. doi: 10.1016/j.ijporl.2011.12.020. Epub 2012 Jan 26.

PubMed [citation]

PMID:: 22281373

See all PubMed Citations (5)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061493.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	38	not provided	not provided	clinical testing	PubMed (5)

Description

The p.Leu90Pro variant in GJB2 is a common, well-known pathogenic variant for au tosomal recessive nonsyndromic hearing loss (Cryns 2004). The p.Leu90Pro variant has been identified in 0.12% (151/126606) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs8033894 5). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency for hearing l oss. In summary, this variant meets criteria to be classified as pathogenic for non-syndromic hearing loss in an autosomal recessive manner. ACMG/AMP Criteria a pplied: PM3_VeryStrong; PS3; PP1; PP3.

#	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		38	not provided	33	not provided

Last Updated: Nov 3, 2024

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