ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.*2G>A (rs150914702)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000176720 SCV000228426 uncertain significance not provided 2017-04-12 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282047 SCV001160027 uncertain significance none provided 2020-04-08 criteria provided, single submitter clinical testing The CFTR c.*2G>A variant (rs150914702), also known as c.4575+2G>A or 4443+2G>A, is reported in the literature in multiple individuals affected with chronic pancreatitis (Audrezet 2002, Steiner 2011). This variant is reported in ClinVar (Variation ID: 53155), and is found in the African population with an allele frequency of 0.18% (46/24914 alleles) in the Genome Aggregation Database. This variant occurs in the 3' untranslated region at a nucleotide that is moderately conserved, but the effect on the poly(a) signal is unknown. Due to limited information, the clinical significance of the c.*2G>A variant is uncertain at this time. References: Audrezet MP et al. Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis. Eur J Hum Genet. 2002 Feb;10(2):100-6. Steiner B et al. Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Hum Mutat. 2011 Aug;32(8):912-20.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001002168 SCV001362319 likely benign not specified 2021-03-12 criteria provided, single submitter clinical testing Variant summary: CFTR c.*2G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.00017 in 276872 control chromosomes, predominantly at a frequency of 0.0018 within the African subpopulation in the gnomAD database. This frequency is not higher than expected for a pathogenic variant in CFTR causing CFTR-related diseases (0.0018 vs 0.013), allowing no conclusion about variant significance. c.*2G>A has been reported in the literature in individuals affected with idiopathic chronic pancreatitis, chronic obstructive pulmonary disease and CF-like symptoms (Solomon_2016, Steiner_2011, Mutesa_2009, Audrezet_2002). Furthermore, in one of these reports the authors conclude that the variant is "not reported to cause CF" (Solomon_2016). Therefore, these data do not allow any conclusion about variant significance. Co-occurrence with two other pathogenic variants in a specimen from a patient undergoing testing for CF has been observed in our laboratory (CFTR c.1521_1523delCTT, p.Phe508del; CFTR c.2290C>T, p.Arg764X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. In summary, no conclusive evidence supporting a pathogenic outcome has been ascertained over a span of 5 years since its initial classification at our laboratory. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV001409872 SCV001611906 likely benign Cystic fibrosis 2020-12-04 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000176720 SCV001714852 uncertain significance not provided 2020-11-20 criteria provided, single submitter 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.