ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.6961-1G>T

dbSNP: rs2136637204
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002030172 SCV002111902 likely pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2023-03-07 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 50 of the CEP290 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with CEP290-related conditions (PMID: 30902645). ClinVar contains an entry for this variant (Variation ID: 1346749). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004536360 SCV004117807 likely pathogenic CEP290-related disorder 2022-10-31 criteria provided, single submitter clinical testing The CEP290 c.6961-1G>T variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant was reported in the heterozygous state in an individual with sporadic retinitis pigmentosa; no second variant was identified in that patient (Martin-Merida et al. 2019. PubMed ID: 30902645). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. Other variants that disrupt consensus splice sites in CEP290 as well as other predicted loss-of-function variants have been reported up- and downstream of this location in patients with CEP290-related disorders (Human Gene Mutation Database, HGMD). Therefore, this variant is interpreted as likely pathogenic.

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