Submissions for variant NM_025114.4(CEP290):c.6135A>G (p.Ser2045=)

dbSNP: rs2035114777

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001296087	SCV001485042	uncertain significance	Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis	2022-06-20	criteria provided, single submitter	clinical testing	This sequence change affects codon 2045 of the CEP290 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CEP290 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). 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: 1000014). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Natera, Inc.	RCV001835395	SCV002091850	uncertain significance	Leber congenital amaurosis	2020-03-13	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004733236	SCV005364876	likely benign	CEP290-related disorder	2022-09-30	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).