Variant NM_000492.4:c.2855T>C


Variant details:
Name NM_000492.4:c.2855T>C
Protein name NP_000483.3:p.(Met952Thr)
Genomic name (hg19) chr7:g.117243783T>C    UCSC    gnomAD
#Exon/intron exon 17
Legacy Name M952T
Class VUS
Subclass VUS5
WT sequence GTGTCGAAAATTTTACACCACAAAA T GTTACATTCTGTTCTTCAAGCACCT
Mutant sequence GTGTCGAAAATTTTACACCACAAAA C GTTACATTCTGTTCTTCAAGCACCT


External sources:
dbSNP
rs142773283


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Hatton et al., 2022 34949556 ✓ ✓


« ✓ » 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
C45 0.00018 0.01 0.992
VUS4 VUS5 VUS5 VUS5

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




2 individuals carrying this variant are reported in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 4
Asymptomatic compound heterozygote 1
CFTR-RD2
  • Aquagenic palmoplantar keratoderma  1
  • Bronchiectasis  1
Pending (NBS) 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Bronchiectasis 5200heterozygoteCF-causing - Trans
VUS3- Undef
Pending (NBS) 1522heterozygoteCF-causing - Trans
Aquagenic palmoplantar keratoderma 5467heterozygoteCF-causing - Trans
Asymptomatic compound heterozygote 5333heterozygoteCFTR-RD-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.