ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.5885G>A (p.Arg1962Lys)

gnomAD frequency: 0.00001  dbSNP: rs562477272
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001247983 SCV001421440 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1962 of the CEP290 protein (p.Arg1962Lys). This variant is present in population databases (rs562477272, gnomAD 0.06%). 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: 972051). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEP290 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.
GeneDx RCV001760286 SCV001990624 uncertain significance not provided 2019-03-25 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002499432 SCV002779586 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2024-03-11 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV003887972 SCV004707645 likely benign Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Natera, Inc. RCV001835317 SCV002091857 uncertain significance Leber congenital amaurosis 2020-05-22 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004538524 SCV004749839 uncertain significance CEP290-related disorder 2024-08-30 no assertion criteria provided clinical testing The CEP290 c.5885G>A variant is predicted to result in the amino acid substitution p.Arg1962Lys. This variant has been reported in an individual with retinitis pigmentosa (Table S9, Koyanagi et al. 2019. PubMed ID: 31213501) and an individual with retinal dystrophy (Table S3, Zhu et al. 2023. PubMed ID: 36493848). However, this variant is reported in 0.079% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/), which may be too frequent to be a primary cause of disease. Although we suspect that c.5885G>A may be benign, the clinical significance of this variant is currently classified as uncertain due to the absence of conclusive functional and genetic evidence.

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