U.S. flag

An official website of the United States government

NM_004004.6(GJB2):c.645del (p.Arg216fs) AND Rare genetic deafness

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 2, 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:
RCV000603609.4

Allele description [Variation Report for NM_004004.6(GJB2):c.645del (p.Arg216fs)]

NM_004004.6(GJB2):c.645del (p.Arg216fs)

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.645del (p.Arg216fs)
HGVS:
  • NC_000013.11:g.20188938del
  • NG_008358.1:g.9039del
  • NM_004004.5:c.645del
  • NM_004004.6:c.645delMANE SELECT
  • NP_003995.2:p.Arg216fs
  • LRG_1350t1:c.645del
  • LRG_1350:g.9039del
  • LRG_1350p1:p.Arg216fs
  • NC_000013.10:g.20763076delA
  • NC_000013.10:g.20763077del
  • NM_004004.5:c.645delT
  • p.Arg216AspfsX18
Protein change:
R216fs
Links:
dbSNP: rs1555341794
NCBI 1000 Genomes Browser:
rs1555341794
Molecular consequence:
  • NM_004004.6:c.645del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000712156Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Jun 2, 2016) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided21not providednot providednot providedclinical testing

Citations

PubMed

Phenotype/genotype correlations in a DFNB1 cohort with ethnical diversity.

Angeli SI.

Laryngoscope. 2008 Nov;118(11):2014-23. doi: 10.1097/MLG.0b013e31817fb7ad.

PubMed [citation]
PMID:
18758381

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, SCV000712156.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

The p.Arg216AspfsExtX6 variant in GJB2 has been reported in 1 individual with no nsyndromic hearing loss (Angeli 2008), and was absent from large population stud ies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 216 and leads to a new termination co don 18 amino acids downstream, thus resulting in a longer protein (the abnormal protein is 6 amino acids longer than the normal protein). In summary, although a dditional studies are required to fully establish its clinical significance, thi s variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided1not provided

Last Updated: Jun 23, 2024