ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2909_2924dup

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557902 SCV000625743 likely pathogenic Cystic fibrosis 2017-08-22 criteria provided, single submitter clinical testing This sequence change duplicates 16 nucleotides in exon 18 of the CFTR mRNA (c.2909_2924dup), including part of the canonical splice site. It is expected to either cause a frameshift at codon 976, followed by a premature translational stop signal (p.Phe976Trpfs*4), or to have no protein effect, due to utilization of a newly created alternate splice site. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with CFTR-related disease (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Experimental studies have not been reported for this variant. If the canonical splice site is maintained and the duplicated sequence is translated, then this variant is expected to result in an absent or disrupted CFTR protein product. However, if the canonical splice site is not used, alternative splicing using the newly created splice site would likely have no effect on the translated protein. 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.
Ambry Genetics RCV001016932 SCV001177941 likely pathogenic Inborn genetic diseases 2019-10-09 criteria provided, single submitter clinical testing The c.2909_2924dup16 variant, located in coding exon 18 of the CFTR gene, results from a duplication of GTGGGATTCTTAATAG at nucleotide position 2909. This 16 nucleotide duplication is expected to cause a translational frameshift with a predicted alternate stop codon (p.F976Wfs*4), which would result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, this duplication could also create a new alternate acceptor site, which would produce a normal protein if used. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Natera, Inc. RCV000557902 SCV001461250 likely pathogenic Cystic fibrosis 2020-09-16 no assertion criteria provided clinical testing

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