ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3468+2dup

dbSNP: rs1554392800
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000576486 SCV000677602 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Eurofins Ntd Llc (ga) RCV000726994 SCV000704794 likely pathogenic not provided 2016-12-27 criteria provided, single submitter clinical testing
Mendelics RCV000576486 SCV000886225 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000576486 SCV001362680 pathogenic Cystic fibrosis 2022-01-27 criteria provided, single submitter clinical testing Variant summary: CFTR c.3468+2dupT (also called as 3600+2insT or c.3468+2_3468+3insT, according to an older nomenclature) alters a 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: four predict the variant abolishes a 5' splicing donor site. At least one publication reported experimental evidence confirming in a mini-gene assay that this variant affects mRNA splicing, and demonstrated no detectable protein in transfected HEK293 cells (Joynt_2020). The variant was absent in 250770 control chromosomes (gnomAD). c.3468+2dupT has been reported in the literature in multiple individuals affected with Cystic Fibrosis (e.g. Van Biervliet 2007, Krenkova 2012, Zietkiewicz 2014, Medza_2021). These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories (including an expert panel, CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all laboratories classified the variant as pathogenic/likely pathogenic, and the expert panel has classified the variant pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000576486 SCV002574079 pathogenic Cystic fibrosis 2022-09-05 criteria provided, single submitter curation This variant was identified in 7 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1, PS3_SUP, PM2_SUP, PM3_VSTR, PP4
Baylor Genetics RCV003465284 SCV004215760 likely pathogenic Bronchiectasis with or without elevated sweat chloride 1 2022-11-17 criteria provided, single submitter clinical testing
Natera, Inc. RCV000576486 SCV001461262 pathogenic Cystic fibrosis 2020-09-16 no assertion criteria provided clinical testing

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