NM_005267.5(GJA8):c.262C>G (p.Pro88Ala) AND Cataract 1 multiple types

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2019
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:: RCV000805199.9

Allele description [Variation Report for NM_005267.5(GJA8):c.262C>G (p.Pro88Ala)]

NM_005267.5(GJA8):c.262C>G (p.Pro88Ala)

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.262C>G (p.Pro88Ala)

HGVS:

NC_000001.11:g.147908217C>G
NG_016242.1:g.10399C>G
NM_005267.5:c.262C>GMANE SELECT
NP_005258.2:p.Pro88Ala
NC_000001.10:g.147380344C>G
NM_005267.4:c.262C>G

Protein change:

P88A

Links:

dbSNP: rs80358200

NCBI 1000 Genomes Browser:

rs80358200

Molecular consequence:

NM_005267.5:c.262C>G - 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
SCV000945146	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2019)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9497259, 19073179, 12800976, 18587493, 16397066, 24535056, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000945146

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2019)

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

A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q.

Shiels A, Mackay D, Ionides A, Berry V, Moore A, Bhattacharya S.

Am J Hum Genet. 1998 Mar;62(3):526-32.

PubMed [citation]

PMID:: 9497259
PMCID:: PMC1376956

The cytoplasmic accumulations of the cataract-associated mutant, Connexin50P88S, are long-lived and form in the endoplasmic reticulum.

Lichtenstein A, Gaietta GM, Deerinck TJ, Crum J, Sosinsky GE, Beyer EC, Berthoud VM.

Exp Eye Res. 2009 Mar;88(3):600-9. doi: 10.1016/j.exer.2008.11.024. Epub 2008 Dec 6.

PubMed [citation]

PMID:: 19073179
PMCID:: PMC2695785

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000945146.6

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

Description

This variant disrupts the p.Pro88 amino acid residue in GJA8. Other variant(s) that disrupt this residue have been observed in individuals with GJA8-related conditions (PMID: 9497259, 19073179, 12800976, 18587493, 16397066, 24535056), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual affected with bilateral cataract (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 88 of the GJA8 protein (p.Pro88Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine.

#	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: Oct 20, 2024

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