ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4C>T (p.Pro2Ser)

gnomAD frequency: 0.00001  dbSNP: rs1064795491
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478865 SCV000571349 uncertain significance not provided 2017-04-11 criteria provided, single submitter clinical testing The P2S variant in the CEP290 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P2S variant was not observed in approximately 5900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P2S 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 P2S as a variant of uncertain significance.
Invitae RCV001373838 SCV001570570 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2 of the CEP290 protein (p.Pro2Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). 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: 421994). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Natera, Inc. RCV001835818 SCV002094950 uncertain significance Leber congenital amaurosis 2019-10-28 no assertion criteria provided clinical testing

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