ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.3368-2A>G (rs755416052)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000169111 SCV000245940 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000169111 SCV000220312 likely pathogenic Cystic fibrosis 2014-05-13 criteria provided, single submitter literature only
Mendelics RCV000169111 SCV000886329 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781260 SCV000919170 pathogenic not specified 2018-12-26 criteria provided, single submitter clinical testing Variant summary: CFTR c.3368-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 245656 control chromosomes (gnomAD). c.3368-2A>G has been reported in the literature in individuals affected with Cystic Fibrosis (Dankert-Roelse_2018, Kharrazi_2015, Sontag_2009, Kammesheidt_2006, Keyeux_2003, ). A ClinVar submission from a reputable database, CFTR2 (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000169111 SCV000932082 pathogenic Cystic fibrosis 2020-02-06 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 20 of the CFTR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs755416052, ExAC 0.009%). This variant has been observed in individuals with cystic fibrosis (PMID: 23974870, 16963320, 26708955). In the literature, this variant is also known as c.3500-2A>G. ClinVar contains an entry for this variant (Variation ID: 188783). 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). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001004496 SCV001163541 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing

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