NM_000165.5(GJA1):c.53C>A (p.Ser18Ter) AND Oculodentodigital dysplasia, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 20, 2022
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:: RCV001210770.7

Allele description [Variation Report for NM_000165.5(GJA1):c.53C>A (p.Ser18Ter)]

NM_000165.5(GJA1):c.53C>A (p.Ser18Ter)

Gene:

GJA1:gap junction protein alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q22.31

Genomic location:

Preferred name:

NM_000165.5(GJA1):c.53C>A (p.Ser18Ter)

HGVS:

NC_000006.12:g.121446900C>A
NG_008308.1:g.16302C>A
NM_000165.5:c.53C>AMANE SELECT
NP_000156.1:p.Ser18Ter
LRG_1289t1:c.53C>A
LRG_1289:g.16302C>A
LRG_1289p1:p.Ser18Ter
NC_000006.11:g.121768046C>A
NM_000165.4:c.53C>A

Protein change:

S18*

Links:

dbSNP: rs1773898086

NCBI 1000 Genomes Browser:

rs1773898086

Molecular consequence:

NM_000165.5:c.53C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Oculodentodigital dysplasia, autosomal recessive
Synonyms:: OCULODENTOOSSEOUS DYSPLASIA, AUTOSOMAL RECESSIVE; ODDD, AUTOSOMAL RECESSIVE; ODOD, AUTOSOMAL RECESSIVE
Identifiers:: MONDO: MONDO:0009768; MedGen: C2749477; Orphanet: 2710; OMIM: 257850

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001382275	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 20, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16816024, 23606748, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001382275

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 20, 2022)

germline

clinical testing

PubMed (3)
[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

A nonsense mutation in the first transmembrane domain of connexin 43 underlies autosomal recessive oculodentodigital syndrome.

Richardson RJ, Joss S, Tomkin S, Ahmed M, Sheridan E, Dixon MJ.

J Med Genet. 2006 Jul;43(7):e37.

PubMed [citation]

PMID:: 16816024
PMCID:: PMC2564566

Autosomal recessive GJA1 (Cx43) gene mutations cause oculodentodigital dysplasia by distinct mechanisms.

Huang T, Shao Q, MacDonald A, Xin L, Lorentz R, Bai D, Laird DW.

J Cell Sci. 2013 Jul 1;126(Pt 13):2857-66. doi: 10.1242/jcs.123315. Epub 2013 Apr 19.

PubMed [citation]

PMID:: 23606748

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001382275.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJA1 protein in which other variant(s) (p.Arg33*) have been determined to be pathogenic (PMID: 16816024, 23606748). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 941060). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive oculodentodigital dysplasia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser18*) in the GJA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 365 amino acid(s) of the GJA1 protein.

#	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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