ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.3251G>A (p.Arg1084Gln)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002770304 SCV003029146 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-05-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1084 of the CEP290 protein (p.Arg1084Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CEP290-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
New York Genome Center RCV003228097 SCV003925238 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5 2022-08-02 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004529169 SCV004109432 uncertain significance CEP290-related disorder 2023-04-28 criteria provided, single submitter clinical testing The CEP290 c.3251G>A variant is predicted to result in the amino acid substitution p.Arg1084Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0042% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-88487605-C-T). 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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