ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.2667G>T (p.Leu889Phe)

gnomAD frequency: 0.00049  dbSNP: rs142038791
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001074451 SCV001240035 uncertain significance Retinal dystrophy 2017-05-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001246474 SCV001419832 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 889 of the CEP290 protein (p.Leu889Phe). This variant is present in population databases (rs142038791, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of CEP290-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 866437). 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 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 RCV001585977 SCV001820374 uncertain significance not provided 2021-11-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002505664 SCV002813275 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-04-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV001828537 SCV002094281 uncertain significance Leber congenital amaurosis 2020-02-02 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004528377 SCV004111772 uncertain significance CEP290-related disorder 2024-08-21 no assertion criteria provided clinical testing The CEP290 c.2667G>T variant is predicted to result in the amino acid substitution p.Leu889Phe. TThis variant has been reported in a patient affected by autosomal dominant rod dystrophy, who was positive for a heterozygous nonsense variant in the PRPF8 gene (Wang et al. 2014. PubMed ID: 25097241, Tables 2 & S3, Patient 38). This variant is reported in 0.13% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, 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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