ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2052dupA (p.Gln685Thrfs) (rs121908746)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000029493 SCV000071473 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Invitae RCV000029493 SCV000074543 pathogenic Cystic fibrosis 2019-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln685Thrfs*4) in the CFTR gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs746460279, ExAC 0.006%). This variant has been reported in individuals affected with cystic fibrosis (PMID: 7525450, 23974870, 24586523), pancreatitis (PMID: 22020151), and congenital absence of the vas deferens (PMID: 9272157). This variant is also known as 2184insA and c.2052_2053insA in the literature. ClinVar contains an entry for this variant (Variation ID: 35838). 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.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000152995 SCV000281418 pathogenic not provided 2015-09-11 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000152995 SCV000331553 pathogenic not provided 2013-12-03 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000029493 SCV000584082 pathogenic Cystic fibrosis 2017-09-14 criteria provided, single submitter research
Ambry Genetics RCV000624094 SCV000742212 pathogenic Inborn genetic diseases 2014-06-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Mendelics RCV000029493 SCV000886185 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Johns Hopkins Genomics,Johns Hopkins University RCV000029493 SCV000999218 pathogenic Cystic fibrosis 2019-05-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002474 SCV001160422 pathogenic not specified 2019-03-22 criteria provided, single submitter clinical testing The CFTR c.2052dupA; p.Gln685fs variant (rs121908786), also known as 2184insA, is reported in the literature in multiple individuals affected with the pancreatic insufficient form of cystic fibrosis (Amato 2012, Doerk 1994, Makukh 2010, Ooi 2012, Sosnay 2013, CFTR2 database). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 35838), and it is found on only seven chromosomes (7/249012 alleles) in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the p.Gln685fs variant is considered to be pathogenic. References: CFTR2 database: http://cftr2.org Amato F et al. Extensive molecular analysis of patients bearing CFTR-related disorders. J Mol Diagn. 2012 Jan;14(1):81-9. Doerk T et al. Detection of more than 50 different CFTR mutations in a large group of German cystic fibrosis patients. Hum Genet. 1994; 94(5):533-42. Makukh H et al. A high frequency of the Cystic Fibrosis 2184insA mutation in Western Ukraine: genotype-phenotype correlations, relevance for newborn screening and genetic testing. J Cyst Fibros. 2010; 9(5):371-5. Ooi C. et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012; 11(5):355-62. 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.
Baylor Genetics RCV001004283 SCV001163159 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV000029493 SCV001169526 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Myriad Women's Health, Inc. RCV000029493 SCV001194227 pathogenic Cystic fibrosis 2019-11-12 criteria provided, single submitter clinical testing NM_000492.3(CFTR):c.2052dupA(Q685Tfs*4, aka 2184insA) is classified as pathogenic in the context of cystic fibrosis and is associated with the classic form of disease. Sources cited for classification include the following: PMID: 23974870. Classification of NM_000492.3(CFTR):c.2052dupA(Q685Tfs*4, aka 2184insA) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Integrated Genetics/Laboratory Corporation of America RCV000029493 SCV000052144 pathogenic Cystic fibrosis 2015-06-10 no assertion criteria provided clinical testing

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