Total submissions: 11
| 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 | |
| Genomic Medicine Center of Excellence, |
RCV000046385 | SCV004808191 | uncertain significance | Cystic fibrosis | 2024-03-29 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003473460 | SCV004213386 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2024-03-30 | criteria provided, single submitter | clinical testing | |
| 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) |
| Labcorp Genetics |
RCV000046385 | SCV002267945 | likely pathogenic | Cystic fibrosis | 2024-10-21 | 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 altered 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 produces a non-functional protein and/or introduces a premature termination codon (PMID: 7518409). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000046385 | SCV001338125 | likely pathogenic | Cystic fibrosis | 2024-12-16 | 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. At least one publication reports experimental evidence that this variant affects mRNA splicing. The variant allele was found at a frequency of 2.4e-05 in 250574 control chromosomes. 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). ClinVar contains an entry for this variant (Variation ID: 53317). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV000046385 | SCV001173070 | likely pathogenic | Cystic fibrosis | 2025-01-03 | 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, functional studies showed that the variant results in skipping of exon 3 (Bienvenu T et al. Hum. Genet., 1994 Jul;94:65-8; Leman R et al. Nucleic Acids Res, 2018 Sep;46:7913-7923; Joynt AT et al. PLoS Genet, 2020 Oct;16:e1009100). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| CFTR- |
RCV001009538 | SCV001169633 | pathogenic | Cystic fibrosis; CFTR-related disorder | 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 |
| Baylor Genetics | RCV001004227 | SCV001163103 | pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | criteria provided, single submitter | clinical testing | ||
| Counsyl | RCV000046385 | SCV000220698 | likely pathogenic | Cystic fibrosis | 2014-09-17 | criteria provided, single submitter | literature only | |
| Baylor Genetics | RCV000046385 | SCV002583265 | likely pathogenic | Cystic fibrosis | no assertion criteria provided | clinical testing |