Variant NM_000492.4:c.2260G>A


Variant details:
Name NM_000492.4:c.2260G>A
Protein name NP_000483.3:p.(Val754Met)
Genomic name (hg19) chr7:g.117232481G>A    UCSC    gnomAD
#Exon/intron exon 14
Legacy Name V754M
Class non disease-causing
complex allele in 20.00% of patients associated with
  • c.[165-291_1585-8528delins39;2619+2288_2989-839delins16] - p.? : 100.00%
    • WT sequence AGAGGCGATACTGCCTCGCATCAGC G TGATCAGCACTGGCCCCACGCTTCA
    Mutant sequence AGAGGCGATACTGCCTCGCATCAGC A TGATCAGCACTGGCCCCACGCTTCA


    External sources:
    dbSNP
    rs150157202


    Functional studies:


    Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
    Sosnay et al, 2013 23974870 ✓ ✓
    Bergougnoux et al, 2015 25797027 ✓ ✓


    « ✓ » indicates the type of analysis performed and not the results




    Pathogenicity predictions:
    AGVGD MAPP SIFT PPH2
    C0 0.4061 0.26 0.014
    VUS1 VUS1 VUS1 VUS1

    Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing




    No patient found in CFTR-NGS catalogue


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

    TOTAL NUMBER OF PATIENTS 15
    Asymptomatic compound heterozygote 2
    CF 3
    CFTR-RD9
    • Bronchiectasis  5
    • CBAVD  1
    • Other  1
    • Pancreatitis  2
    Pending 1



    Detailed genotypes:
    Phenotype Patient ID Variant status Additional variants
    Bronchiectasis 5126heterozygoteCFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    CFTR-RD-causing- Undef
    Bronchiectasis 4488heterozygotevarying clinical consequence - Trans
    Bronchiectasis 2424heterozygote
    Bronchiectasis 1846heterozygoteVUS1- Undef
    Bronchiectasis 1810heterozygoteVUS3- Undef
    VUS1- Undef
    CF 2096heterozygoteCF-causing- Undef
    CF-causing- Undef
    CF 2029heterozygoteCF-causing - Cis
    CF-causing - Trans
    CF 5811heterozygoteCF-causing- Undef
    CF-causing- Undef
    CBAVD 1296heterozygoteCFTR-RD-causing- Undef
    VUS1- Undef
    CF-causing- Undef
    Pancreatitis 1712heterozygoteCF-causing- Undef
    varying clinical consequence- Undef
    Pancreatitis 1656heterozygotevarying clinical consequence- Undef
    Asymptomatic compound heterozygote 4758heterozygoteCF-causing - Trans
    Asymptomatic compound heterozygote 4757heterozygoteCF-causing - Trans
    Other 4293heterozygoteVUS1 - Trans
    Pending 4548heterozygoteCF-causing - Trans


    Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing



                CFTR variants are clustered into five groups:
    • 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.