Variant NM_000492.4:c.2421A>G


Variant details:
Name NM_000492.4:c.2421A>G
Protein name NP_000483.3:p.(Ile807Met)
Genomic name (hg19) chr7:g.117232642A>G    UCSC    gnomAD
#Exon/intron exon 14
Legacy Name I807M ; 2553A/G
Class disease-causing
Subclass CFTR-RD-causing
complex allele in 22.22% of patients associated with
  • c.4056G>T - p.(Gln1352His) : 100.00%
    • WT sequence AGGCAAACTTGACTGAACTGGATAT A TATTCAAGAAGGTTATCTCAAGAAA
    Mutant sequence AGGCAAACTTGACTGAACTGGATAT G TATTCAAGAAGGTTATCTCAAGAAA


    External sources:
    866
    767
    		 dbSNP
    rs1800103


    Functional studies:


    Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
    Vankeerberghen et al, 1998 9736778 ✓ ✓


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


    Response to modulators:


    Modulator FDA approval EMA approval in vitro / ex vivo data clinical data
    IVA yesnoyesno
    TEZ-IVA yesnoyesno
    ELX-TEZ-IVA yesnoyesno


    clinical and functional data are provided by Vertex


    Pathogenicity predictions:
    AGVGD MAPP SIFT PPH2
    C0 0.00116 0.01 0.996
    VUS1 VUS5 VUS5 VUS5

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




    No patient found in CFTR-NGS catalogue


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

    TOTAL NUMBER OF PATIENTS 9
    Asymptomatic compound heterozygote 2
    CFTR-RD7
    • CBAVD  3
    • Other  1
    • Pancreatitis  3



    Detailed genotypes:
    Phenotype Patient ID Variant status Additional variants
    CBAVD 927heterozygoteVUS4 - Cis
    CF-causing - Trans
    CBAVD 4247heterozygoteCF-causing- Undef
    VUS4- Undef
    CBAVD 4248heterozygoteCF-causing- Undef
    VUS4- Undef
    Asymptomatic compound heterozygote 932heterozygoteVUS4 - Cis
    CF-causing - Trans
    Asymptomatic compound heterozygote 5133heterozygoteVUS3- Undef
    Pancreatitis 1632heterozygoteCF-causing- Undef
    Pancreatitis 2185heterozygote
    Pancreatitis 2252heterozygoteCF-causing- Undef
    Other 4587heterozygote


    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.