Total submissions: 30
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
American College of Medical Genetics and Genomics |
RCV000007645 | SCV000071402 | pathogenic | Cystic fibrosis | 2004-03-03 | practice guideline | curation | Converted during submission to Pathogenic. |
CFTR2 | RCV000007645 | SCV000071456 | pathogenic | Cystic fibrosis | 2017-03-17 | reviewed by expert panel | research | |
Labcorp Genetics |
RCV000007645 | SCV000074751 | pathogenic | Cystic fibrosis | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 18 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). This variant is present in population databases (rs75096551, gnomAD 0.1%). Disruption of this splice site has been observed in individuals with cystic fibrosis, and is included in the American College of Medical Genetics (ACMG) panel of CF variants (PMID: 15371902, 23974870). This variant is also known as 3120+1G>A. ClinVar contains an entry for this variant (Variation ID: 7224). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Eurofins Ntd Llc |
RCV000759761 | SCV000226734 | pathogenic | not provided | 2016-12-27 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000007645 | SCV000603044 | pathogenic | Cystic fibrosis | 2024-05-26 | criteria provided, single submitter | clinical testing | The CFTR c.2988+1G>A variant (rs75096551), also known as 3120+1G>A, is reported in patients diagnosed with cystic fibrosis (Chavez-Saldana 2010, Masekela 2013, Wilschanski 1995), and is associated with elevated sweat levels and pancreatic insufficiency (Masekela 2013, Ooi 2012, Sosnay 2013, see CFTR2 database). This variant is reported in ClinVar (Variation ID: 7224), and is found in the general population with an overall allele frequency of 0.01% (33/282364 alleles) in the Genome Aggregation Database. This variant disrupts the canonical splice donor site of intron 18, which is likely to negatively impact gene function. Functional characterization indicates that exon 18 is skipped in the CFTR mRNA, and results in the absence of CFTR protein (Sharma 2014). Based on available information, this variant is considered to be pathogenic. References: CFTR2 database link: https://cftr2.org/ Chavez-Saldana M et al. CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening. Rev Invest Clin. 2010; 62(6):546-52. PMID: 21416780 Masekela R et al. Phenotypic expression of the 3120+1G>A mutation in non-Caucasian children with cystic fibrosis in South Africa. J Cyst Fibros. 2013; 12(4):363-6. PMID: 23206872 Ooi C. et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012; 11(5):355-62. PMID: 22658665 Sharma N et al. Experimental assessment of splicing variants using expression minigenes and comparison with in silico predictions. Hum Mutat. 2014; 35(10):1249-59. PMID: 25066652 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. PMID: 23974870 Wilschanski M et al. Correlation of sweat chloride concentration with classes of the cystic fibrosis transmembrane conductance regulator gene mutations. J Pediatr. 1995; 127(5):705-10. PMID: 7472820 |
Genomic Research Center, |
RCV000007645 | SCV000784252 | pathogenic | Cystic fibrosis | 2018-03-05 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759761 | SCV000889304 | pathogenic | not provided | 2020-04-11 | criteria provided, single submitter | clinical testing | The pathogenic c.2988+1G>A variant (also known as 3120+1G>A) is located in a canonical splice-donor site and interferes with/prevents normal CFTR mRNA splicing (PMID: 25066652 (2014)). It is a known CF pathogenic variant associated with pancreatic insufficiency, and has been reported in individuals affected with CF in the published literature (PMIDs: 9683582 (1998), 9950364 (1999), 23206872 (2013), and 23974870 (2013)). |
Department Of Genetics, |
RCV000007645 | SCV000891677 | pathogenic | Cystic fibrosis | 2017-12-30 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000763580 | SCV000894419 | pathogenic | Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000007645 | SCV001137489 | pathogenic | Cystic fibrosis | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001004285 | SCV001163161 | pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
CFTR- |
RCV000007645 | SCV001169503 | pathogenic | Cystic fibrosis | 2018-01-29 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV000007645 | SCV001194076 | pathogenic | Cystic fibrosis | 2019-11-12 | criteria provided, single submitter | clinical testing | NM_000492.3(CFTR):c.2988+1G>A(aka 3120+1G>A) 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.2988+1G>A(aka 3120+1G>A) is based on the following criteria: The variant is located at a canonical splice site, is expected to disrupt gene function and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. |
Baylor Genetics | RCV000007645 | SCV001523283 | pathogenic | Cystic fibrosis | 2019-09-26 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Mayo Clinic Laboratories, |
RCV000759761 | SCV001714239 | pathogenic | not provided | 2024-07-09 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000759761 | SCV002019242 | pathogenic | not provided | 2021-06-18 | criteria provided, single submitter | clinical testing | |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000007645 | SCV002512247 | pathogenic | Cystic fibrosis | 2021-08-20 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 moderate, PM3 strong |
Ambry Genetics | RCV000007645 | SCV002751244 | pathogenic | Cystic fibrosis | 2022-02-09 | criteria provided, single submitter | clinical testing | The c.2988+1G>A pathogenic mutation (also known as 3120+1G>A in published literature), is located one nucleotide after coding exon 18 of the CFTR gene. This is one of the most common pathogenic mutations in African American individuals with cystic fibrosis (CF) (Zampoli On Behalf Of The Msac M. S. Afr. Med. J., 2018 Dec;109:16-19). In one study, this mutation was identified in ten affected African American individuals with pancreatic insufficiency (PI) and elevated sweat chloride levels (Macek M Am. J. Hum. Genet. 1997 May;60(5):1122-7). This pathogenic mutation was further described in four African American individuals, one who was homozygous and three compound heterozygous with another mutation. All individuals demonstrated compromised lung function, elevated sweat chloride levels, and PI (Carles S et al. J. Med. Genet. 1996 Sep;33(9):802-4). A functional in vitro study of splice site alterations in CFTR noted this mutation generated no detectable CFTR protein (Sharma N et al Hum. Mutat. 2014 Oct;35(10):1249-59). 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 pathogenic. |
Al Jalila Children’s Genomics Center, |
RCV000007645 | SCV002818169 | pathogenic | Cystic fibrosis | 2024-10-04 | criteria provided, single submitter | research | PVS1, PM3_VeryStrong, PM2, PP4, PS3 |
Division of Human Genetics, |
RCV000007645 | SCV004034122 | pathogenic | Cystic fibrosis | 2023-07-01 | criteria provided, single submitter | research | |
Baylor Genetics | RCV003473046 | SCV004213277 | pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2024-03-28 | criteria provided, single submitter | clinical testing | |
Genomic Medicine Center of Excellence, |
RCV000007645 | SCV004807375 | pathogenic | Cystic fibrosis | 2024-03-26 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000007645 | SCV000027846 | pathogenic | Cystic fibrosis | 1998-08-01 | no assertion criteria provided | literature only | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000007645 | SCV000052162 | pathogenic | Cystic fibrosis | 2015-06-22 | no assertion criteria provided | clinical testing | |
Natera, |
RCV001027899 | SCV001190622 | pathogenic | CFTR-related disorder | 2019-05-20 | no assertion criteria provided | clinical testing | |
Gene |
RCV000007645 | SCV001622803 | not provided | Cystic fibrosis | no assertion provided | literature only | ||
Diagnostic Laboratory, |
RCV000759761 | SCV001741020 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000759761 | SCV001957727 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000759761 | SCV001966485 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
RCV001027899 | SCV004118258 | pathogenic | CFTR-related disorder | 2024-09-28 | no assertion criteria provided | clinical testing | The CFTR c.2988+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has previously been reported to be causative for cystic fibrosis (Wilschanski et al. 1995. PubMed ID: 7472820; Sosnay et al. 2013. PubMed ID: 23974870). This variant is reported in 0.12% of alleles in individuals of African descent in gnomAD. Variants that disrupt the consensus splice donor site in CFTR are expected to be pathogenic. This variant is interpreted as pathogenic. |