Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| CFTR2 | RCV000046385 | SCV000924237 | uncertain significance | Cystic fibrosis | 2020-01-10 | reviewed by expert panel | research | |
| Counsyl | RCV000046385 | SCV000220698 | likely pathogenic | Cystic fibrosis | 2014-09-17 | criteria provided, single submitter | literature only | |
| Baylor Genetics | RCV001004227 | SCV001163103 | pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
| CFTR- |
RCV001009538 | SCV001169633 | pathogenic | Cystic fibrosis; CFTR-related disorders | 2015-07-01 | criteria provided, single submitter | curation | the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both |
| Ambry Genetics | RCV000046385 | SCV001173070 | likely pathogenic | Cystic fibrosis | 2022-05-26 | criteria provided, single submitter | clinical testing | The c.165-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 3 in the CFTR gene. This variant was detected in conjunction with a second CFTR alteration in a 44-year-old woman with cystic fibrosis who presented with elevated sweat chloride levels, pulmonary symptoms, and pancreatic sufficiency; however, the pathogenicity of the second alteration was uncertain (Bienvenu T et al. Hum. Genet., 1994 Jul;94:65-8). This alteration was also reported in a fetus with meconium ileus who had p.F508del (Oca F et al. Clin. Chem., 2009 Dec;55:2214-7). In addition, another variant at the same nucleotide position (c.165-3C>A) has been reported in an individual with pulmonary disease, pancreatic insufficiency, and high sweat chloride level; this individual carried p.F508del on the other chromosome (Strandvik B et al. Genet. Test., 2001;5:235-42). In vitro analysis of c.165-3C>T showed abnormal RNA splicing and protein expression (Bienvenu T et al. Hum. Genet., 1994 Jul;94:65-8; The Clinical and Functional TRanslation of CFTR (CFTR2), available at http://cftr2.org, accessed <April 11, 2018>). This nucleotide position is highly conserved in available vertebrate species. This alteration is predicted by ESEfinder to weaken the efficacy of the native acceptor splice site. Using the Human Splicing Finder (HSF) splice site prediction tool, this alteration is also predicted to weaken the native splice acceptor site. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000046385 | SCV001338125 | likely pathogenic | Cystic fibrosis | 2023-12-14 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.165-3C>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant weakens a 3 acceptor site. Several functional studies report this variant affects mRNA splicing and results in exon 3 skipping (Bienvenu_1994, Leman_2018, Joynt_2020). The variant allele was found at a frequency of 2.4e-05 in 250574 control chromosomes (gnomAD). c.165-3C>T has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Bienvenu_1994, Oca_2009, Kharrazi_2015). These data indicate that the variant may be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 10923036, 19833837, 7550227, 10982968, 7518409, 8947061, 25087612, 26574590, 29750258, 16617247, 32126153, 31036917, 32256364, 33085659, 34996830, 34196078). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=1) and likely pathogenic (n=3) and pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV000046385 | SCV002267945 | likely pathogenic | Cystic fibrosis | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the CFTR gene. It does not directly change the encoded amino acid sequence of the CFTR protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs200337193, gnomAD 0.005%). This variant has been observed in individual(s) with cystic fibrosis (PMID: 19833837). This variant is also known as 297-3C>T. ClinVar contains an entry for this variant (Variation ID: 53317). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 3 and introduces a premature termination codon (PMID: 7518409). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV003233099 | SCV003930979 | likely pathogenic | not provided | 2023-06-09 | criteria provided, single submitter | clinical testing | Classified as a variant of uncertain significance in a well curated database (CFTR2); Published functional studies demonstrate abnormal splicing resulting in aberrant transcript lacking exon 3 as well as some residual full-length transcript (Leman et al., 2018; Joynt et al., 2020); A different variant at this position, c.165-3C>A (reported as 297-3C>A), has been identified in an individual with clinical features of cystic fibrosis who also carried a pathogenic CFTR variant (Strandvik et al., 2001); In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Also known as 297-3C>T; This variant is associated with the following publications: (PMID: 28603918, 7550227, 7518409, 29750258, 16617247, 31036917, 8947061, 25087612, 19833837, 26574590, 32126153, 10923036, 32256364, 10982968, 34782259, 11788090, 34996830, 33085659) |
| Baylor Genetics | RCV003473460 | SCV004213386 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-09-14 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000046385 | SCV002583265 | likely pathogenic | Cystic fibrosis | no assertion criteria provided | clinical testing |