Structural eye disease

Gene: EPHA2

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 1:56 p.m. | Last Modified: 2 May 2024, 1:56 p.m.

Panel Version: 3.79

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

Comment on mode of inheritance: PMID: 35918037 highlights that both monoallelic and biallelic EPHA2 variants are responsible for the phenotypes reported in table 1, therefore, the mode of inheritance for EPHA2 should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review.

Created: 19 Oct 2023, 4:48 p.m. | Last Modified: 19 Oct 2023, 4:48 p.m.

Panel Version: 3.40

EPHA2 variants are associated with Cataract 6, multiple types (OMIM:116600) and as definitive Gen2Phen gene for the same condition. PMID: 35918037 presents a review numerous EPHA2 variants and their associated phenotypes, together with a report of a syndromic complex microphthalmia with iris hypoplasia caused compound heterozygous EPHA2 variants. Various ocular features are reported, including microphthalmia, congenital cataracts, nystagmus, microcornea (PMID: 35918037, table 1).

Created: 19 Oct 2023, 4:45 p.m. | Last Modified: 19 Oct 2023, 5:07 p.m.

Panel Version: 3.40

I don't know

PMID: 35918037 report a boy with bilateral microphthalmia and anterior segment malformation including microcornea and congenital cataract, who was found to have 2 mutations in EPHA2 - p.Trp14* and a heterozygous 17 kb deletion that encompasses intron 3 to exon 17 of EPHA2. Mother confirmed to carry deletion, father not available for testing

Created: 15 Sep 2023, 11:05 a.m. | Last Modified: 15 Sep 2023, 11:05 a.m.

Panel Version: 3.4

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Bilateral microphthalmia; microcornea; congenital cataract

Publications

• 35918037

I don't know

Harding et al. 2021 report two unrelated multi-generation families with microphthalmia and cataract with a missense or splice site variant segregating in affected members. No inheritance for second variant and no data supporting splicing effect. Variants have previously been found in families with cataracts. They also demonstrate that morpholino knockdown of EPHA2b in zebrafish caused microphthalmia. Varsome: missense = VUS; splice variant=pathogenic

Created: 20 Jan 2022, 11:38 a.m. | Last Modified: 20 Jan 2022, 11:38 a.m.

Panel Version: 1.101

RH

Created: 19 Jun 2019, 3:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cataract 6, multiple types; Cataract 6, multiple types 116600; 116600

Publications

• 33671840

Red List (low evidence)

Comment on list classification: Promoted from Red to Amber. There is currently not enough evidence to support a gene-disease association.

Created: 1 Mar 2022, 3:43 p.m. | Last Modified: 1 Mar 2022, 3:43 p.m.

Panel Version: 1.108

Submitted on behalf of Professor Nicola Ragge (Wessex and West Midlands GLH). RH

Created: 17 Apr 2019, 3:31 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cataract 6, multiple types; 116600

Variants in this GENE are reported as part of current diagnostic practice