ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.869+5G>A (rs533959068)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668284 SCV000792858 uncertain significance Cystic fibrosis 2017-07-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781277 SCV000919190 likely pathogenic not specified 2018-05-24 criteria provided, single submitter clinical testing Variant summary: CFTR c.869+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 5' splicing donor site and two predict the variant weakens a 5' donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Raynal_2013). The variant allele was found at a frequency of 8.2e-06 in 243092 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing CFTR-related diseases (8.2e-06 vs 1.30e-02), allowing no conclusion about variant significance. The variant, c.869+5G>A, has been reported in the literature in individuals affected with CF and CBAVD (Girardet_2007, Goh_2007). These data indicate that the variant may be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. The CFTR-France database cites the variant in a CF patient with classification of 'disease-causing' and UMD and Sickkids cite the variant in a CF patient with deltaF508 in trans. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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