Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CFTR2 | RCV000411056 | SCV001981567 | pathogenic | Cystic fibrosis | 2021-09-24 | reviewed by expert panel | research | |
| Counsyl | RCV000411056 | SCV000486002 | likely pathogenic | Cystic fibrosis | 2016-03-14 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV000411056 | SCV002574104 | pathogenic | Cystic fibrosis | 2022-09-05 | criteria provided, single submitter | curation | This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1, PM2_SUP, PM3 |
| Labcorp Genetics |
RCV000411056 | SCV002933648 | likely pathogenic | Cystic fibrosis | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 6 of the CFTR 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 CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 370635). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000411056 | SCV004020668 | likely pathogenic | Cystic fibrosis | 2023-06-07 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.744-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: two predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 213646 control chromosomes (gnomAD). c.744-2A>G has been reported in the literature in individuals affected with Cystic Fibrosis, including those with pancreatic insufficiency (e.g., McCague_2019, Deletang_2022). These reports suggest the variant may be associated with Cystic Fibrosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 35650428, 30888834). Four ClinVar submitters (evaluation after 2014) have cited the variant, and all submitters classified the variant as pathogenic (n = 2) or likely pathogenic (n = 2). Based on the evidence outlined above, the variant was classified as likely pathogenic. |