NM_004004.6(GJB2):c.2T>G (p.Met1Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2023
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:: RCV003688870.2

Allele description [Variation Report for NM_004004.6(GJB2):c.2T>G (p.Met1Arg)]

NM_004004.6(GJB2):c.2T>G (p.Met1Arg)

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.2T>G (p.Met1Arg)

Other names:

NM_004004.6(GJB2):c.2T>G; p.Met1Arg

HGVS:

NC_000013.11:g.20189580A>C
NG_008358.1:g.8396T>G
NM_004004.6:c.2T>GMANE SELECT
NP_003995.2:p.Met1Arg
LRG_1350t1:c.2T>G
LRG_1350:g.8396T>G
LRG_1350p1:p.Met1Arg
NC_000013.10:g.20763719A>C
NM_004004.5:c.2T>G

Protein change:

M1R

Links:

dbSNP: rs371086981

NCBI 1000 Genomes Browser:

rs371086981

Molecular consequence:

NM_004004.6:c.2T>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_004004.6:c.2T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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At.1154 AND (alive[prop]) (1)
Gene
SAC9 sacI homology domain-containing protein / WW domain-containing protein [Ara...
SAC9 sacI homology domain-containing protein / WW domain-containing protein [Arabidopsis thaliana]
Gene ID:825146

Gene
RecName: Full=DET1- and DDB1-associated protein 1; AltName: Full=Placenta cross-...
RecName: Full=DET1- and DDB1-associated protein 1; AltName: Full=Placenta cross-immune reaction antigen 1; Short=PCIA-1
gi|74733400|sp|Q9BW61.1|DDA1_HUMAN

Protein
Leukoencephalopathy with vanishing white matter 3
Leukoencephalopathy with vanishing white matter 3

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004431302	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12189493, 9482292, 10218527, 18941476, 20146813, 29605365, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004431302

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2023)

germline

clinical testing

PubMed (7)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Human connexin26 (GJB2) deafness mutations affect the function of gap junction channels at different levels of protein expression.

Thönnissen E, Rabionet R, Arbonès ML, Estivill X, Willecke K, Ott T.

Hum Genet. 2002 Aug;111(2):190-7. Epub 2002 Jun 22.

PubMed [citation]

PMID:: 12189493

Connexin-26 mutations in sporadic and inherited sensorineural deafness.

Estivill X, Fortina P, Surrey S, Rabionet R, Melchionda S, D'Agruma L, Mansfield E, Rappaport E, Govea N, Milà M, Zelante L, Gasparini P.

Lancet. 1998 Feb 7;351(9100):394-8.

PubMed [citation]

PMID:: 9482292

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004431302.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of the initiator codon alters GJB2 gene expression (PMID: 12189493). ClinVar contains an entry for this variant (Variation ID: 551915). Disruption of the initiator codon has been observed in individuals with autosomal recessive non-syndromic deafness (PMID: 9482292, 10218527, 18941476, 20146813, 29605365). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the GJB2 mRNA. The next in-frame methionine is located at codon 34.

#	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: Sep 29, 2024

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