ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.2551G>A (p.Val851Ile)

gnomAD frequency: 0.00001  dbSNP: rs764963626
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228050 SCV000290912 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 851 of the CEP290 protein (p.Val851Ile). This variant is present in population databases (rs764963626, gnomAD 0.07%). 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: 241583). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics RCV000763866 SCV000894800 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2022-02-01 criteria provided, single submitter clinical testing
GeneDx RCV002274949 SCV002562550 likely benign not provided 2022-08-10 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Ambry Genetics RCV002518359 SCV003724931 likely benign Inborn genetic diseases 2021-06-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
New York Genome Center RCV003227727 SCV003925134 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5 2022-05-06 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004529413 SCV004108222 uncertain significance CEP290-related disorder 2024-02-01 criteria provided, single submitter clinical testing The CEP290 c.2551G>A variant is predicted to result in the amino acid substitution p.Val851Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.075% of alleles in individuals of Latino descent in gnomAD, which may be too frequent to be an unreported primary cause of disease. 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.
Natera, Inc. RCV001271583 SCV001452850 uncertain significance Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.