ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.1766+3A>G (rs397508298)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000056354 SCV000071569 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000301070 SCV000331668 pathogenic not provided 2016-05-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000056354 SCV000696868 pathogenic Cystic fibrosis 2017-06-13 criteria provided, single submitter clinical testing Variant summary: The CFTR c.1766+3A>G (legacy name: 1898+3A>G) variant involves the alteration of a conserved intronic nucleotide and 3/4 splice prediction tools predict an impact on normal splicing. A functional study, Dujardin_2011, found the variant to cause exon 12 skipping through a mini-gene system. This variant is absent in 119766 control chromosomes (ExAC). Multiple publications have cited the variant in affected individuals, along with multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Mendelics RCV000056354 SCV000886223 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
CFTR-France RCV000056354 SCV001169433 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Invitae RCV000056354 SCV001574185 likely pathogenic Cystic fibrosis 2020-05-20 criteria provided, single submitter clinical testing This sequence change falls in intron 13 of the CFTR gene. It does not directly change the encoded amino acid sequence of the CFTR protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with cystic fibrosis (PMID: 18178635, 15480987). This variant is also known as 1898+3A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 53379). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 21317048). 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.
Counsyl RCV000056354 SCV001132153 pathogenic Cystic fibrosis 2019-06-27 no assertion criteria provided clinical testing

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