ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.2423A>G (p.Tyr808Cys)

gnomAD frequency: 0.00001  dbSNP: rs773007151
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000685413 SCV000812892 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-04-06 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 808 of the CEP290 protein (p.Tyr808Cys). This variant is present in population databases (rs773007151, gnomAD 0.01%). 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: 565773). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Genome-Nilou Lab RCV001526757 SCV001737281 uncertain significance Joubert syndrome 5 2021-06-10 criteria provided, single submitter clinical testing
GeneDx RCV001561418 SCV001784021 uncertain significance not provided 2020-07-15 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001275032 SCV001459786 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004535703 SCV004741041 uncertain significance CEP290-related disorder 2024-02-21 no assertion criteria provided clinical testing The CEP290 c.2423A>G variant is predicted to result in the amino acid substitution p.Tyr808Cys. This variant was reported in the homozygous state in an individual with intellectual disability and ADHD (Arteche-López et al. 2021. PubMed ID: 33921431). This variant is reported in 0.014% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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