Submissions for variant NM_000492.4(CFTR):c.2012del (p.Ser670_Leu671insTer)

dbSNP: rs121908812

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000029491	SCV000071470	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000029491	SCV000074534	pathogenic	Cystic fibrosis	2024-05-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu671*) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). This variant is present in population databases (rs758077237, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with cystic fibrosis (PMID: 1283149, 20659818, 22658665, 23276700, 23974870, 24586523). This variant is also known as 2143delT. ClinVar contains an entry for this variant (Variation ID: 35836). For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV000029491	SCV000886209	pathogenic	Cystic fibrosis	2018-11-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001004281	SCV001163157	pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
CFTR-France	RCV000029491	SCV001169421	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000029491	SCV001194019	pathogenic	Cystic fibrosis	2019-12-09	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.2012delT(L671*, aka 2143delT) 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.2012delT(L671*, aka 2143delT) 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.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000029491	SCV001934295	pathogenic	Cystic fibrosis	2022-09-05	criteria provided, single submitter	curation	This variant was identified in 3 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1, PM2_SUP, PM3_VSTR
Ambry Genetics	RCV000029491	SCV002720296	pathogenic	Cystic fibrosis	2022-08-01	criteria provided, single submitter	clinical testing	The c.2012delT pathogenic mutation (also known as p.L671* and 2143delT), located in coding exon 14 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 2012, changes the amino acid from a leucine to a stop codon within coding exon 14. This pathogenic mutation was first described in 6 German individuals who were compound heterozygous for another pathogenic mutation in the CFTR gene; clinical symptoms included severe pulmonary disease, pancreatic insufficiency, and elevated sweat chloride levels (Dörk T et al. Hum. Genet., 1992 Nov;90:279-84). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Revvity Omics, Revvity	RCV001530162	SCV003820728	pathogenic	not provided	2022-02-03	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000029491	SCV004024522	pathogenic	Cystic fibrosis	2023-06-06	criteria provided, single submitter	clinical testing	Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Baylor Genetics	RCV003473131	SCV004213260	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-11-04	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001530162	SCV005625704	pathogenic	not provided	2024-10-23	criteria provided, single submitter	clinical testing	The CFTR c.2012del (p.Leu671*) variant causes the premature termination of CFTR protein synthesis. This variant has been reported in the published literature in individuals with cystic fibrosis (PMIDs: 1283149 (1992), 20659818 (2010), 23276700 (2013), 32429104 (2020), and 38003474 (2023)). It has also been reported in individuals with pancreatic insufficiency (PMIDs: 18456578 (2008) and 22658665 (2012)), as well as in congenital bilateral absence of the vas deferens (CBAVD) (PMID: 38003474 (2023)). Based on the available information, this variant is classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005031459	SCV005673349	pathogenic	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2024-06-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000029491	SCV005878758	pathogenic	Cystic fibrosis	2024-01-09	criteria provided, single submitter	clinical testing	The CFTR c.2012del; p.Leu671Ter variant (rs121908812), also known as 2143delT for legacy nomenclature, is reported as a common CF-causing allele in Eastern European populations (Castellani 2008, Dork 1992, Petrova 2020), and is commonly associated with pancreatic insufficiency (CFTR2 database). This variant is only found on three alleles in the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to CFTR2 database: https://cftr2.org/ Castellani C et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros. 2008 May;7(3):179-96. PMID: 18456578. Dork T et al. A termination mutation (2143delT) in the CFTR gene of German cystic fibrosis patients. Hum Genet. 1992 Nov;90(3):279-84. PMID: 1283149. Petrova NV et al. Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients. Genes (Basel). 2020 May 15;11(5):554. PMID: 32429104.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029491	SCV000052142	pathogenic	Cystic fibrosis	2015-04-03	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001027915	SCV001190638	pathogenic	CFTR-related disorder		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001530162	SCV001744904	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001530162	SCV001957230	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001530162	SCV001975289	pathogenic	not provided		no assertion criteria provided	clinical testing