ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.7340A>C (p.Lys2447Thr)

gnomAD frequency: 0.00006  dbSNP: rs201382524
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001075283 SCV001240899 uncertain significance Retinal dystrophy 2017-09-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001242969 SCV001416095 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 2447 of the CEP290 protein (p.Lys2447Thr). This variant is present in population databases (rs201382524, 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: 866908). 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: "Benign"; 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.
GeneDx RCV002290589 SCV002578770 uncertain significance not provided 2022-09-12 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
Ambry Genetics RCV003353155 SCV004063910 uncertain significance Inborn genetic diseases 2023-08-08 criteria provided, single submitter clinical testing The c.7340A>C (p.K2447T) alteration is located in exon 54 (coding exon 53) of the CEP290 gene. This alteration results from a A to C substitution at nucleotide position 7340, causing the lysine (K) at amino acid position 2447 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252440 SCV001428196 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing
Natera, Inc. RCV001828540 SCV002091807 uncertain significance Leber congenital amaurosis 2020-02-07 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004528379 SCV004111658 uncertain significance CEP290-related disorder 2024-01-09 no assertion criteria provided clinical testing The CEP290 c.7340A>C variant is predicted to result in the amino acid substitution p.Lys2447Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% 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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