VCV001300168.2 - ClinVar

NM_000492.4(CFTR):c.[3846G>A;3848G>T]

Germline

Top reviewed classifications are shown here.

Submission summary:

1 submission

1 submitter

1 condition

Reviewed by expert panel

Pathogenic

Jan 2020 by CFTR2

for Cystic fibrosis

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_000492.4(CFTR):c.[3846G>A;3848G>T]

Other names: p.[Trp1282X;Arg1283Met]
Functional consequence: -
Links: -

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CFTR		-	-	GRCh38 GRCh37	3825	5200

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Cystic fibrosis	Pathogenic (1)	reviewed by expert panel	Jan 10, 2020	RCV001731145.11

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 10, 2020)	reviewed by expert panel (Submitter's publication and website) Method: research	Cystic fibrosis Affected status: yes Allele origin: germline	CFTR2 Accession: SCV001981594.1 First in ClinVar: Oct 25, 2021 Last updated: Oct 25, 2021	Other databases https://cftr2.org https://cftr2.org

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients.	Petrova NV	Genes	2020	PMID: 32429104
Ataluren/ivacaftor combination therapy: Two N-of-1 trials in cystic fibrosis patients with nonsense mutations.	Peabody Lever JE	Pediatric pulmonology	2020	PMID: 32281737
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.	Hou YC	Proceedings of the National Academy of Sciences of the United States of America	2020	PMID: 31980526
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.	Capalbo A	PLoS genetics	2019	PMID: 31589614
Sequencing as a first-line methodology for cystic fibrosis carrier screening.	Beauchamp KA	Genetics in medicine : official journal of the American College of Medical Genetics	2019	PMID: 31036917
Cystic fibrosis in Tunisian children: a review of 32 children.	Boussetta K	African health sciences	2018	PMID: 30602999
High-frequency actionable pathogenic exome variants in an average-risk cohort.	Rego S	Cold Spring Harbor molecular case studies	2018	PMID: 30487145
S737F is a new CFTR mutation typical of patients originally from the Tuscany region in Italy.	Terlizzi V	Italian journal of pediatrics	2018	PMID: 29298718
Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.	Archibald AD	Genetics in medicine : official journal of the American College of Medical Genetics	2018	PMID: 29261177
Correctors and Potentiators Rescue Function of the Truncated W1282X-Cystic Fibrosis Transmembrane Regulator (CFTR) Translation Product.	Haggie PM	The Journal of biological chemistry	2017	PMID: 27895116
Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation.	Mutyam V	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2017	PMID: 27707539
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.	Xiong HY	Science (New York, N.Y.)	2015	PMID: 25525159
Disease variants in genomes of 44 centenarians.	Freudenberg-Hua Y	Molecular genetics & genomic medicine	2014	PMID: 25333069
Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.	Tabor HK	American journal of human genetics	2014	PMID: 25087612
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene.	Sosnay PR	Nature genetics	2013	PMID: 23974870
A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients.	Masson E	PloS one	2013	PMID: 23951356
CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders.	Thauvin-Robinet C	Journal of medical genetics	2013	PMID: 23378603
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.	Lazarin GA	Genetics in medicine : official journal of the American College of Medical Genetics	2013	PMID: 22975760
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis.	Ooi CY	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2012	PMID: 22658665
Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens.	Steiner B	Human mutation	2011	PMID: 21520337
CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening.	Chávez-Saldaña M	Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion	2010	PMID: 21416780
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.	McWilliams RR	Cancer	2010	PMID: 19885835
Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.	Farrell PM	The Journal of pediatrics	2008	PMID: 18639722
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice.	Castellani C	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society	2008	PMID: 18456578
Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials.	Wilschanski M	American journal of respiratory and critical care medicine	2006	PMID: 16840743
Genotype-phenotype correlation for pulmonary function in cystic fibrosis.	de Gracia J	Thorax	2005	PMID: 15994263
Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel.	Watson MS	Genetics in medicine : official journal of the American College of Medical Genetics	2004	PMID: 15371902
Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study.	McKone EF	Lancet (London, England)	2003	PMID: 12767731
A clinical perspective of cystic fibrosis and new genetic findings: relationship of CFTR mutations to genotype-phenotype manifestations.	Kulczycki LL	American journal of medical genetics. Part A	2003	PMID: 12503104
Laboratory standards and guidelines for population-based cystic fibrosis carrier screening.	Grody WW	Genetics in medicine : official journal of the American College of Medical Genetics	2001	PMID: 11280952
Severe allergic bronchopulmonary aspergillosis in an infant with cystic fibrosis and her asthmatic father.	Mussaffi H	Pediatric pulmonology	2000	PMID: 10639207
The association of nonsense codons with exon skipping.	Valentine CR	Mutation research	1998	PMID: 9806422
Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.	Cohn JA	The New England journal of medicine	1998	PMID: 9725922
Congenital bilateral absence of vas deferens with a new missense mutation (P499A) in the CFTR gene.	Arduino C	Clinical genetics	1998	PMID: 9630075
Cystic fibrosis: genotypic and phenotypic variations.	Zielenski J	Annual review of genetics	1995	PMID: 8825494
Molecular and clinical findings in Austrian cystic fibrosis patients with mutations in exon 11 of the CFTR gene.	Greil I	Wiener klinische Wochenschrift	1995	PMID: 7545856
Two novel mutations in the CFTR gene: W1089X in exon 17B and 4010delTATT in exon 21.	Shoshani T	Human molecular genetics	1994	PMID: 7520798
Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR.	Yang Y	Human molecular genetics	1993	PMID: 7691345
Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease.	Shoshani T	American journal of human genetics	1992	PMID: 1370365
A new missense mutation (R1283M) in exon 20 of the cystic fibrosis transmembrane conductance regulator gene.	Cheadle JP	Human molecular genetics	1992	PMID: 1284468
Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis.	Hamosh A	The Journal of clinical investigation	1991	PMID: 1721624
Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene.	Kerem BS	Proceedings of the National Academy of Sciences of the United States of America	1990	PMID: 2236053
Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis.	Vidaud M	Human genetics	1990	PMID: 2210768
A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.	Cutting GR	Nature	1990	PMID: 1695717
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.	Riordan JR	Science (New York, N.Y.)	1989	PMID: 2475911
Hamosh, A. Personal Communication. 2018. Baltimore, Md.	-	-	-	-
http://www.cftr2.org/	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR	-	-	-	-
https://cftr2.org	-	-	-	-
https://cftr2.org	-	-	-	-
https://cftr2.org	-	-	-	-
https://cftr2.org/mutation/scientific/W1282X/	-	-	-	-
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Text-mined citations for this variant ...

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_000492.4(CFTR):c.[3846G>A;3848G>T]

Variant Details

NM_000492.4(CFTR):c.[3846G>A;3848G>T]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...