ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.7392_7393insCA (p.Glu2465fs)

dbSNP: rs757255407
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001241131 SCV001414126 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-11-01 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the CEP290 gene (p.Glu2465Glnfs*21). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 15 amino acid(s) of the CEP290 protein and extend the protein by 5 additional amino acid residues. This variant is present in population databases (rs757255407, gnomAD 0.06%). 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: 966453). This variant disrupts the C-terminus of the CEP290 protein. Other variant(s) that disrupt this region (p.Glu2465Valfs*2) have been observed in individuals with CEP290-related conditions (PMID: 34196655). This suggests that this may be a clinically significant region of the protein. 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 RCV001586081 SCV001813187 uncertain significance not provided 2023-06-16 criteria provided, single submitter clinical testing Frameshift variant in which the last 15 amino acids are replaced with 20 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533, 34196655)
Preventiongenetics, part of Exact Sciences RCV003414046 SCV004108233 uncertain significance CEP290-related condition 2023-07-18 criteria provided, single submitter clinical testing The CEP290 c.7392_7393insCA variant is predicted to result in a frameshift and premature protein termination (p.Glu2465Glnfs*21). This variant is located in the last exon of coding and is expected to disrupt the final 16 amino acids. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.058% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88443008-C-CTG). Although frameshift variants are known to be pathogenic, nearly all occur upstream of this variant. Therefore, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001828967 SCV002091802 uncertain significance Leber congenital amaurosis 2020-01-27 no assertion criteria provided clinical testing

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