ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1624G>T (p.Gly542Ter) (rs113993959)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
American College of Medical Genetics and Genomics (ACMG) RCV000007535 SCV000071394 pathogenic Cystic fibrosis 2004-03-03 practice guideline curation Converted during submission to Pathogenic.
CFTR2 RCV000007535 SCV000071540 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
PharmGKB RCV000417172 SCV000494682 drug response ataluren response - Efficacy 2016-03-23 reviewed by expert panel curation PharmGKB Level of Evidence 2A: Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
Invitae RCV000007535 SCV000074376 pathogenic Cystic fibrosis 2018-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly542*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs113993959, ExAC 0.04%). This variant is recognized as a common cause of cystic fibrosis (PMID: 15371902, 23974870). In the literature, this variant is also known as G542X. ClinVar contains an entry for this variant (Variation ID: 7115). Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000058931 SCV000225524 pathogenic not provided 2015-10-12 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000058931 SCV000281000 pathogenic not provided 2015-02-11 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000007535 SCV000584080 pathogenic Cystic fibrosis 2018-04-16 criteria provided, single submitter research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000058931 SCV000603003 pathogenic not provided 2017-10-19 criteria provided, single submitter clinical testing The CFTR p.Gly542Ter (G542X) variant has been reported in numerous patients diagnosed with cystic fibrosis, and is often associated with pancreatic insufficiency (Kerem 1990, Sosnay 2013, CFTR2 database). REFERENCES CFTR2 database: Kerem B et al. Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc Natl Acad Sci U S A. 1990; 87(21):8447-51. Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013; 45(10):1160-7.
Integrated Genetics/Laboratory Corporation of America RCV000007535 SCV000696855 pathogenic Cystic fibrosis 2016-01-21 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000007535 SCV000883110 pathogenic Cystic fibrosis 2018-11-21 criteria provided, single submitter clinical testing
Mendelics RCV000007535 SCV000886177 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000058931 SCV000889294 pathogenic not provided 2015-11-17 criteria provided, single submitter clinical testing
Center for Precision Medicine,Vanderbilt University Medical Center RCV000007535 SCV000889997 pathogenic Cystic fibrosis 2018-03-16 criteria provided, single submitter research
Fulgent Genetics,Fulgent Genetics RCV000763572 SCV000894411 pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral absence of the vas deferens 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000007535 SCV000915203 pathogenic Cystic fibrosis 2017-10-25 criteria provided, single submitter clinical testing The CFTR c.1624G>T (p.Gly542Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Gly542Ter variant, a well-described pathogenic variant, is reported at a frequency of 2.64% among a pan-ethnic population clinically diagnosed with CFTR-related disorders, and recognised as the second most common pathogenic variant after p.Phe508del (Watson et al. 2004). The p.Gly542Ter variant is one of the 23 pathogenic variants recommended by the ACMG for general population cystic fibrosis carrier screening. Across a selection of the available literature, the p.Gly542Ter variant was identified in at least 40 individuals with cystic fibrosis, including five unrelated individuals in a homozygous state, 11 unrelated individuals in a compound heterozygous state, and 24 individuals in a heterozygous state (de Gracia et al. 2005; Chavez-Saldana et al. 2010). Five of the compound heterozygotes carried p.Phe508del on the second allele (de Gracia et al. 2005). Control data were unavailable for this variant in these studies but it is reported at a frequency of 0.001860 in the European American population of the Exome Sequencing Project. Based on the evidence and the potential impact of stop-gained variants, the p.Gly542Ter variant is classified as pathogenic for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000007535 SCV000027736 pathogenic Cystic fibrosis 1997-06-01 no assertion criteria provided literature only
SNPedia RCV000058931 SCV000090452 not provided not provided no assertion provided not provided
GeneReviews RCV000119041 SCV000153747 pathogenic Hereditary pancreatitis 2014-03-13 no assertion criteria provided literature only
Counsyl RCV000007535 SCV000485211 pathogenic Cystic fibrosis 2015-11-24 no assertion criteria provided clinical testing

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