ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.165-2A>G

dbSNP: rs397508250
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
CFTR-France RCV001009517 SCV001169612 pathogenic Cystic fibrosis; CFTR-related disorder 2018-01-29 criteria provided, single submitter curation the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both
Institute of Human Genetics, University of Leipzig Medical Center RCV002284359 SCV002574063 pathogenic Cystic fibrosis 2022-09-05 criteria provided, single submitter curation This variant was identified in 2 unrelated patients 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, PP4
Ambry Genetics RCV002284359 SCV002704174 pathogenic Cystic fibrosis 2021-10-08 criteria provided, single submitter clinical testing The c.165-2A>G intronic pathogenic mutation, also known as 297-2A>G, results from an A to G substitution two nucleotides before coding exon 3 in the CFTR gene. This variant (reported as 297-2A>G) was detected in two siblings with clinical presentations of cystic fibrosis: a male with meconium ileus and lung disease who died at the age of 3 months, and a female with a positive sweat chloride test, pancreatic insufficiency, severe lung disease and P. aeruginosa colonization before 3 years of age. The mutation was heterozygous and found to be in trans with c.2463_2464del (p.S821fs, also known as 2594delGT) on the other chromosome (Visich A et al. Clin. Genet., 2002 Mar;61:207-13). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. In addition to the clinical data presented in the literature, 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 a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV002284359 SCV004684914 pathogenic Cystic fibrosis 2022-12-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 53315). This variant is also known as 297-2A>G. Disruption of this splice site has been observed in individuals with cystic fibrosis (PMID: 10798368, 12000363, 16980811). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 2 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).

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.