ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.3858C>A (p.Phe1286Leu)

gnomAD frequency: 0.00001  dbSNP: rs1353300022
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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 RCV000528258 SCV000634652 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-06-20 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1286 of the CEP290 protein (p.Phe1286Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 461783). 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 C15"). 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 RCV002483397 SCV002784861 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-04-18 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004537949 SCV004119990 uncertain significance CEP290-related disorder 2023-03-14 criteria provided, single submitter clinical testing The CEP290 c.3858C>A variant is predicted to result in the amino acid substitution p.Phe1286Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0024% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88482980-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV004772962 SCV005384233 uncertain significance not provided 2024-01-05 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001271576 SCV001452842 uncertain significance Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing

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