Structural eye disease
Gene: EPHA2
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
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 testingCreated: 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
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=pathogenicCreated: 20 Jan 2022, 11:38 a.m. | Last Modified: 20 Jan 2022, 11:38 a.m.
Panel Version: 1.101
RHCreated: 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
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). RHCreated: 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
Mode of inheritance for gene: EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q4_23_promote_green tag was added to gene: EPHA2. Tag Q4_23_MOI tag was added to gene: EPHA2. Tag Q4_23_NHS_review tag was added to gene: EPHA2.
Publications for gene: EPHA2 were set to
Phenotypes for gene: EPHA2 were changed from Cataract 6, multiple types, 116600 to Cataract 6, multiple types, OMIM:116600
Gene: epha2 has been classified as Amber List (Moderate Evidence).
gene: EPHA2 was added gene: EPHA2 was added to Structural eye disease. Sources: NHS GMS Mode of inheritance for gene: EPHA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: EPHA2 were set to Cataract 6, multiple types, 116600