ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.551A>G (p.Gln184Arg)

gnomAD frequency: 0.00002  dbSNP: rs374752439
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482317 SCV000571001 uncertain significance not provided 2019-01-16 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CEP290 gene. The Q184R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The Q184R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001865461 SCV002207242 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2021-12-15 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 184 of the CEP290 protein (p.Gln184Arg). This variant is present in population databases (rs374752439, 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: 421712). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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