ClinVar Miner

Submissions for variant NM_004431.5(EPHA2):c.2162G>A (p.Arg721Gln)

gnomAD frequency: 0.00073  dbSNP: rs116506614
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000368763 SCV000350369 likely benign Cataract 6 multiple types 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Mendelics RCV002247334 SCV002517028 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Invitae RCV000368763 SCV004639042 uncertain significance Cataract 6 multiple types 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 721 of the EPHA2 protein (p.Arg721Gln). This variant is present in population databases (rs116506614, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individuals with cortical cataract (PMID: 19649315, 29267365). ClinVar contains an entry for this variant (Variation ID: 13262). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EPHA2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects EPHA2 function (PMID: 19649315). 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.
OMIM RCV000014172 SCV000034420 pathogenic Cataract 6, age-related cortical 2009-07-01 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442224 SCV000510515 likely pathogenic Cortical senile cataract 2016-05-13 no assertion criteria provided literature only

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