ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.4242+2T>C

dbSNP: rs193922526
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029539 SCV000052191 likely pathogenic Cystic fibrosis 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Ambry Genetics RCV000029539 SCV002630543 likely pathogenic Cystic fibrosis 2017-11-14 criteria provided, single submitter clinical testing The c.4242+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 26 in the CFTR gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000029539 SCV004675881 pathogenic Cystic fibrosis 2023-01-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). ClinVar contains an entry for this variant (Variation ID: 35884). Disruption of this splice site has been observed in individual(s) with cystic fibrosis (PMID: 1379210, 7682196, 15074370). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 26 of the CFTR gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Natera, Inc. RCV000029539 SCV001456317 likely pathogenic Cystic fibrosis 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.