ClinVar

Description

Variant summary: CFTR c.889C>T (p.Arg297Trp) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 250500 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CFTR causing Non-Classic Cystic Fibrosis (4.8e-05 vs 0.013), allowing no conclusion about variant significance. c.889C>T has been reported in the literature as a compound heterozygous genotype with the 5T allele on the background of a homozygous c.4056G>C (p.Gln1352His) genotype in an individual affected with CBAVD (Dork_1997). This finding is interpreted as a complex allele in cis with c.4056G>C (p.Gln1352His). It has also been reported as a non-informative (second allele not specified) genotype in an individual with chronic pancreatitis (CP) (Sultan_2012). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 9272157, 19810821, 22094894, 26277102). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.