ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2679G>T (p.Gly893=) (rs397508419)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002013 SCV001159829 likely pathogenic not specified 2018-07-19 criteria provided, single submitter clinical testing The CFTR c.2679G>T; p.Gly893Gly variant (rs397508419), also called c.2811G>T, is reported in the literature in two individuals mildly affected with cystic fibrosis, both of whom carried a second pathogenic CFTR variant (Faa' 2010, Groman 2002). This is a synonymous variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor splice site. Analyses of c.2679G>T variant mRNAs have confirmed these transcripts are aberrantly spliced, leading to an in-frame deletion of 231 nucleotides at the end of exon 15 (Faa' 2010, Groman 2002). This variant is found in the general population with an overall allele frequency of 0.0012% (3/246030 alleles,) in the Genome Aggregation Database. Based on available information, this variant is considered to be likely pathogenic. References: Faa' V et al. A synonymous mutation in the CFTR gene causes aberrant splicing in an italian patient affected by a mild form of cystic fibrosis. J Mol Diagn. 2010 May;12(3):380-3. Groman JD et al. Variant cystic fibrosis phenotypes in the absence of CFTR mutations. N Engl J Med. 2002 Aug 8;347(6):401-7.
Johns Hopkins Genomics,Johns Hopkins University RCV001250515 SCV001425307 uncertain significance Cystic fibrosis 2020-03-09 criteria provided, single submitter clinical testing CFTR c.2679G>T has been identified in patients with features of cystic fibrosis3. A single ClinVar submitter classifies this synonymous variant as likely pathogenic. This CFTR variant (rs397508419) is rare (<0.1%) in a large population dataset (gnomAD: 3/282672 total alleles; 0.0011%; no homozygotes). Bioinformatic analysis predicts that this variant would create a cryptic exon 17 (legacy exon 15) splice donor site. Functional studies indicate that the use of this cryptic donor site produces a misspliced mRNA that is predicted to result in a protein lacking 76 amino acids from exon 17, however the amount of this aberrantly spliced mRNA has not been quantified. Due to insufficient evidence about the functional consequence of this variant, we consider the clinical significance of c.2679G>T to be uncertain at this time.

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.