Submissions for variant NM_012186.3(FOXE3):c.562TACGCGCCC[3] (p.188YAP[3])

dbSNP: rs768610152

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001215819	SCV001387582	uncertain significance	Congenital primary aphakia; Anterior segment dysgenesis	2025-01-27	criteria provided, single submitter	clinical testing	This variant, c.571_579dup, results in the insertion of 3 amino acid(s) of the FOXE3 protein (p.Tyr191_Pro193dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs768610152, gnomAD 0.04%). This variant has been observed in individual(s) with clinical features of FOXE3-related conditions (PMID: 20806047, 33816482). This variant is also known as c.579_580insTACGCGCCC (p.194_195insTyrAlaPro). ClinVar contains an entry for this variant (Variation ID: 945230). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002348719	SCV002650608	uncertain significance	Cardiovascular phenotype	2023-11-17	criteria provided, single submitter	clinical testing	The c.571_579dupTACGCGCCC variant (also known as p.Y191_P193dup), located in coding exon 1 of the FOXE3 gene, results from an in-frame duplication of TACGCGCCC at nucleotide positions 571 to 579. This results in the duplication of 3 extra residues (YAP) between codons 191 and 193. In one study, this variant was reported to co-occur with a PAX6 nonsense alteration in an individual with aniridia, lens opacities, and additional ocular defects (Brémond-Gignac D et al. Mol. Vis., 2010 Aug;16:1705-11). This amino acid region is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702586	SCV001929593	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702586	SCV001968159	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004751923	SCV005346273	uncertain significance	FOXE3-related disorder	2024-06-21	no assertion criteria provided	clinical testing	The FOXE3 c.571_579dup9 variant is predicted to result in an in-frame duplication (p.Tyr191_Pro193dup). This variant was reported in an individual with congenital cataract with aniridia, although this patient also had a likely causative variant in another gene (Brémond-Gignac et al. 2010. PubMed ID: 20806047). This variant is reported in 0.034% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.