ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.2T>A (p.Met1Lys)

gnomAD frequency: 0.00001  dbSNP: rs368984997
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001091344 SCV001247312 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001862693 SCV002201732 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2024-01-11 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the CEP290 mRNA. The next in-frame methionine is located at codon 11. This variant is present in population databases (rs368984997, gnomAD 0.0009%). Disruption of the initiator codon has been observed in individuals with Leber congenital amaurosis and/or Senior-Loken syndrome (PMID: 17345604, 21866095). ClinVar contains an entry for this variant (Variation ID: 871409). This variant disrupts the p.Trp7 amino acid residue in CEP290. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16682970, 27422788). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002482162 SCV002785969 likely pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-04-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004536141 SCV004713632 pathogenic CEP290-related disorder 2023-10-27 criteria provided, single submitter clinical testing The CEP290 c.2T>A variant is predicted to disrupt the translation initiation site (Start Loss). This variant was reported in individuals with Leber congenital amaurosis (Patient 416 in Perrault et al. 2007. PubMed ID: 17345604; Supplemental Table 1 in Weisschuh et al. 2020. PubMed ID: 32531858; Table S2 in Drivas et al. 2015. PubMed ID: 26062849) and in a patient with renal and ophthalmic features (Patient 63 in Best et al. 2022. PubMed ID: 35764379). This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD ( and has been interpreted as likely pathogenic and pathogenic in ClinVar ( Of note, a different variant that disrupts the methionine start codon (c.1A>G) has also been reported in patients with CEP290-related disorders (Patient F57 in Helou. 2007. PubMed ID: 17617513). Based on this evidence, we interpret the c.2T>A (start loss) variant as pathogenic.

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