ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.2620-2A>G

dbSNP: rs1554390859
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630456 SCV000751412 pathogenic Cystic fibrosis 2019-02-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported in combination with another CFTR variant in an individual affected with clinical features of cystic fibrosis (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 15 of the CFTR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Ambry Genetics RCV000630456 SCV002740788 likely pathogenic Cystic fibrosis 2022-03-08 criteria provided, single submitter clinical testing The c.2620-2A>G intronic variant results from an A to G substitution two nucleotides before coding exon 16 in the CFTR gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Natera, Inc. RCV001834985 SCV002080780 pathogenic CFTR-related disorder 2017-03-17 no assertion criteria provided clinical testing

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