NM_005267.5(GJA8):c.263C>A (p.Pro88Gln) AND Cataract 1 multiple types

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002246207.2

Allele description [Variation Report for NM_005267.5(GJA8):c.263C>A (p.Pro88Gln)]

NM_005267.5(GJA8):c.263C>A (p.Pro88Gln)

Gene:

GJA8:gap junction protein alpha 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.2

Genomic location:

Preferred name:

NM_005267.5(GJA8):c.263C>A (p.Pro88Gln)

HGVS:

NC_000001.11:g.147908218C>A
NG_016242.1:g.10400C>A
NM_005267.5:c.263C>AMANE SELECT
NP_005258.2:p.Pro88Gln
NC_000001.10:g.147380345C>A

Protein change:

P88Q

Links:

dbSNP: rs782199122

NCBI 1000 Genomes Browser:

rs782199122

Molecular consequence:

NM_005267.5:c.263C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cataract 1 multiple types
Synonyms:: CATARACT, DUFFY-LINKED; Cataract 1; CATARACT 1, MULTIPLE TYPES, WITH OR WITHOUT MICROCORNEA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007285; MedGen: C1861828; Orphanet: 1377; OMIM: 116200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002515922	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 20, 2022)	unknown	curation	PubMed (3) [See all records that cite these PMIDs] 16397066, 18587493, 25741868
SCV005081739	Dept. Genetics and Cancer, Menzies Institute for Medical Research, University of Tasmania	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 21, 2023)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 16397066, 18587493, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002515922

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 20, 2022)

unknown

curation

PubMed (3)
[See all records that cite these PMIDs]

SCV005081739

Dept. Genetics and Cancer, Menzies Institute for Medical Research, University of Tasmania

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 21, 2023)

germline

curation

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	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

A novel GJA8 mutation is associated with autosomal dominant lamellar pulverulent cataract: further evidence for gap junction dysfunction in human cataract.

Arora A, Minogue PJ, Liu X, Reddy MA, Ainsworth JR, Bhattacharya SS, Webster AR, Hunt DM, Ebihara L, Moore AT, Beyer EC, Berthoud VM.

J Med Genet. 2006 Jan;43(1):e2.

PubMed [citation]

PMID:: 16397066
PMCID:: PMC2564510

A mutation in GJA8 (p.P88Q) is associated with "balloon-like" cataract with Y-sutural opacities in a family of Indian origin.

Vanita V, Singh JR, Singh D, Varon R, Sperling K.

Mol Vis. 2008 Jun 17;14:1171-5.

PubMed [citation]

PMID:: 18587493
PMCID:: PMC2435161

See all PubMed Citations (3)

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV002515922.1

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

Description

This variant is interpreted as likely pathogenic for Cataract 1, multiple types, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (PM5); Located in a mutational hot spot and/or critical and well-established functional domain (PM1).

#	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 Dept. Genetics and Cancer, Menzies Institute for Medical Research, University of Tasmania, SCV005081739.1

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

Description

Variant identified and curated during a GJA8 specific review of the literature in relation to pediatric or congenital cataract. ACMG-AMP criteria applied: PP1(Strong), PS4(Supporting), PM1(Supporting), PM2(Supporting), PM5(Supporting), PP3. Original variant report: PMID:16397066;18587493. The cataract phenotype/s reported for this variant are: Lamellar pulverulent, and Nuclear with feather-like sutural opacity and prominent riders. Gene review and curation guidelines are outlined in: https://doi.org/10.1080/17469899.2023.2160320

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

Last Updated: Jul 23, 2024

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