ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.6023C>T (p.Ala2008Val)

gnomAD frequency: 0.00002  dbSNP: rs376307540
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521358 SCV000620213 uncertain significance not provided 2017-08-31 criteria provided, single submitter clinical testing The A2008V variant in the CEP290 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This 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 A2008V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A2008V as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002527628 SCV003263385 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2008 of the CEP290 protein (p.Ala2008Val). This variant is present in population databases (rs376307540, 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: 451500). 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: "Tolerated"; 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.
Ambry Genetics RCV002528248 SCV003659660 uncertain significance Inborn genetic diseases 2022-11-07 criteria provided, single submitter clinical testing The c.6023C>T (p.A2008V) alteration is located in exon 44 (coding exon 43) of the CEP290 gene. This alteration results from a C to T substitution at nucleotide position 6023, causing the alanine (A) at amino acid position 2008 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001829510 SCV002091854 uncertain significance Leber congenital amaurosis 2020-11-02 no assertion criteria provided clinical testing

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