ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.7070A>G (p.Glu2357Gly)

gnomAD frequency: 0.00003  dbSNP: rs759725378
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484031 SCV000574425 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing The E2357G variant in the CEP290 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E2357G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E2357G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E2357G as a variant of uncertain significance.
Ambry Genetics RCV001265797 SCV001443968 uncertain significance Inborn genetic diseases 2014-06-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001851281 SCV002179830 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-06-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2357 of the CEP290 protein (p.Glu2357Gly). This variant is present in population databases (rs759725378, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 424602). 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 tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV002489183 SCV002790995 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-02-25 criteria provided, single submitter clinical testing
Natera, Inc. RCV001829393 SCV002091820 uncertain significance Leber congenital amaurosis 2019-10-28 no assertion criteria provided clinical testing

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