Updates for c.2855T>C:
2024-10-14 Class updated from VUS5 to unclassified /non-CF
2024-12-09 Variant classified as VUS non-CF on the basis of epidemiological data (in particular high frequency in the general population), the number and type of diagnosis for patients reported in CFTR-France and functional data




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    
Genomic name (hg38) chr7:g.117603729T>C    UCSC
#Exon/intron exon 17
Legacy Name M952T
Class VUS
Subclass non-CF
WT sequence GTGTCGAAAATTTTACACCACAAAA T GTTACATTCTGTTCTTCAAGCACCT
Mutant sequence GTGTCGAAAATTTTACACCACAAAA C GTTACATTCTGTTCTTCAAGCACCT

Other databases:
dbSNP
rs142773283



Pathogenicity predictors:

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
VNZ-TEZ-DIVA yesnoyesno

clinical and functional data presented above are provided by Vertex


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


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

TOTAL NUMBER OF PATIENTS 6
Asymptomatic compound heterozygote 1
CFTR-RD4
  • Aquagenic palmoplantar keratoderma  2
  • Bronchiectasis  1
  • Other  1
Pending (NBS) 1




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

Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Aquagenic palmoplantar keratoderma 6549heterozygoteCF-causing- Undef
Aquagenic palmoplantar keratoderma 5467heterozygoteCF-causing - Trans
Bronchiectasis 5200heterozygoteCF-causing - Trans
VUS3- Undef
Pending (NBS) 1522heterozygoteCF-causing - Trans
Other 6402heterozygoteCF-causing- Undef
Asymptomatic compound heterozygote 5333heterozygoteCFTR-RD-causing - 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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