Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genia |
RCV000855422 | SCV000995021 | pathogenic | Cystic fibrosis | 2019-10-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000855422 | SCV001213618 | pathogenic | Cystic fibrosis | 2019-03-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants 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). Variants that affect this acceptor splice site have been observed in individuals affected with cystic fibrosis (PMID: 15365999, 11668613). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 3 of the CFTR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000855422 | SCV004813617 | likely pathogenic | Cystic fibrosis | 2024-02-12 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.274-5_274-2delTGTA 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: Four predict the variant abolishes a 5' splicing donor site. Two predict the variant creates a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250412 control chromosomes (gnomAD). To our knowledge, no occurrence of c.274-5_274-2delTGTA in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 694030). Based on the evidence outlined above, the variant was classified as likely pathogenic. |