Variant NM_000492.4:c.2538G>A


Variant details:
Name NM_000492.4:c.2538G>A
Protein name NP_000483.3:p.(Trp846*)
Genomic name (hg19)     chr7:g.117235031G>A    UCSC    
Genomic name (hg38) chr7:g.117594977G>A    UCSC
#Exon/intron exon 15
Legacy Name W846X (2670TGG>TGA)
Class disease-causing
Subclass CF-causing
WT sequence AGAGCATACCAGCAGTGACTACATG G AACACATACCTTCGATATATTACTG
Mutant sequence AGAGCATACCAGCAGTGACTACATG A AACACATACCTTCGATATATTACTG

Other databases:
dbSNP
rs267606722







Pathogenicity predictors:

Not found




Response to modulators:


Reference PMID Modulator in vitro / ex vivo data clinical data Patient responsiveness
Burgel et al., 2024 39151434 ELX-TEZ-IVAN.D. yesno



No patient found in CFTR-NGS catalogue


34 patients carrying this variant are reported in CFTR-France:

TOTAL NUMBER OF PATIENTS 34
CF 28
CFTR-RD3
  • CBAVD  3
Pending (NBS) 3




Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   disease-causing

Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 319heterozygoteCF-causing - Trans
CF 3751heterozygoteCF-causing- Undef
CF 3784heterozygoteVUS3- Undef
CF 3951heterozygoteCF-causing- Undef
CF 3956heterozygoteCF-causing- Undef
CF 4026heterozygoteCF-causing - Trans
CF 4185heterozygoteCF-causing- Undef
CF 6502heterozygotevarying clinical consequence- Undef
CF 4298heterozygoteCF-causing- Undef
CF 4364heterozygoteCF-causing - Trans
CF 4365heterozygoteCF-causing - Trans
CF 4441heterozygoteCF-causing - Trans
CF 4442heterozygoteCF-causing - Trans
CF 3747heterozygoteCF-causing- Undef
CF 3725heterozygoteCF-causing - Trans
CF 611heterozygoteCF-causing - Trans
CF 6537heterozygoteCF-causing- Undef
CF 1593heterozygoteCF-causing- Undef
CF 5888heterozygoteCF-causing - Trans
CF 2442heterozygoteCF-causing- Undef
CF 2510heterozygoteCF-causing- Undef
CF 3005heterozygoteCF-causing - Trans
CF 3077heterozygoteCF-causing- Undef
CF 3486heterozygoteCF-causing- Undef
CF 3491heterozygoteCF-causing- Undef
CF 3544heterozygoteCF-causing- Undef
CF 3600heterozygoteCF-causing - Trans
CF 4466heterozygoteCF-causing - Trans
CBAVD 931heterozygoteCFTR-RD-causing - Trans
CBAVD 1373heterozygote
CBAVD 2437heterozygoteCFTR-RD-causing- Undef
Pending (NBS) 3771heterozygotevarying clinical consequence - Trans
Pending (NBS) 3817heterozygotevarying clinical consequence - Trans
Pending (NBS) 3872heterozygotevarying clinical consequence - Trans


Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   disease-causing



            CFTR variants are clustered into five groups (click here for more details about the classification of variants):
  • CF-causing: when in trans with another CF-causing mutation, will result in CF.
  • CFTR-RD causing: when in trans with a CF-causing mutation, will result in CFTR-related disorders (CFTR-RD) such as chronic pancreatitis, bronchiectasis, CRS-NP (chronic rhinosinusitis with or without nasal polyposis) or CBAVD (congenital absence of vas deferens), according to Bombieri C et al., 2011.
  • Varying clinical consequence: when in trans with another CF-causing mutation, can either result in CF or in a CFTR-RD.
  • Non disease-causing: when in trans with a CF-causing mutation, will not cause CF, nor CFTR-RD.
  • VUS (Variant of unknown clinical significance): unclassified because of insufficient data.



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