ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2490+1G>A (rs141158996)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000007595 SCV000071455 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Invitae RCV000007595 SCV000074614 pathogenic Cystic fibrosis 2018-12-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 14 of the CFTR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been observed in several individuals affected with cystic fibrosis (PMID: 7683952, 23974870, 20059485, 12815607) and congenital bilateral absence of the vas deferens (PMID: 9239681). It is also known as 2622+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 7175). 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. 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.
Integrated Genetics/Laboratory Corporation of America RCV000007595 SCV000696902 pathogenic Cystic fibrosis 2016-06-07 criteria provided, single submitter clinical testing Variant summary: The CFTR c.2490+1G>A variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant, and 5/5 splicing algorithms predict the variant to abolish the canonical splice donor site. This variant was found in 2/109598 control chromosomes at a frequency of 0.0000182, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant has been cited in numerous classic CF patients in the literature in trans with pathogenic variants, including deltaF508. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
OMIM RCV000007595 SCV000027796 pathogenic Cystic fibrosis 2018-04-09 no assertion criteria provided literature only
Counsyl RCV000007595 SCV000220959 pathogenic Cystic fibrosis 2015-07-21 no assertion criteria provided clinical testing

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