ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.2587-3C>T

gnomAD frequency: 0.00001  dbSNP: rs759025964
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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 RCV001308201 SCV001497640 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-11-01 criteria provided, single submitter clinical testing This sequence change falls in intron 24 of the CEP290 gene. It does not directly change the encoded amino acid sequence of the CEP290 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs759025964, gnomAD 0.05%). 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: 991347). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV004035490 SCV004926222 uncertain significance Inborn genetic diseases 2023-11-27 criteria provided, single submitter clinical testing The c.2587-3C>T intronic alteration consists of a C to T substitution 3 nucleotides before coding exon 24 in the CEP290 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001279549 SCV001466646 uncertain significance Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004545172 SCV004796218 uncertain significance CEP290-related disorder 2024-04-16 no assertion criteria provided clinical testing The CEP290 c.2587-3C>T variant is predicted to interfere with splicing. This variant is predicted to impact splicing by weakening the acceptor site, based on splicing prediction algorithm (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.049% of alleles in individuals of Latino 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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