ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.6320A>G (p.Lys2107Arg)

gnomAD frequency: 0.00008  dbSNP: rs755933899
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001053430 SCV001217690 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-11-05 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2107 of the CEP290 protein (p.Lys2107Arg). This variant is present in population databases (rs755933899, gnomAD 0.01%). This missense change has been observed in individual(s) with CEP290-related conditions (PMID: 29974258). ClinVar contains an entry for this variant (Variation ID: 849463). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CEP290 protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV005005008 SCV005630410 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2023-12-29 criteria provided, single submitter clinical testing
Natera, Inc. RCV001272015 SCV001453643 uncertain significance Leber congenital amaurosis 2019-12-19 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004536105 SCV004114893 uncertain significance CEP290-related disorder 2024-06-25 no assertion criteria provided clinical testing The CEP290 c.6320A>G variant is predicted to result in the amino acid substitution p.Lys2107Arg. This variant has been reported in the heterozygous state in an individual with Joubert syndrome; however the individual also harbored a variant in the KIF7 gene (patient 1-62, Table S2, Kroes et al. 2016. PubMed ID: 25920555; Table 3, Stokman et al. 2018. PubMed ID: 29974258). This variant is reported in 0.0085% 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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