ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1680-886A>G (rs397508266)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000046417 SCV000071568 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724668 SCV000700815 pathogenic not provided 2017-02-28 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763576 SCV000894415 pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral absence of the vas deferens 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781239 SCV000919144 pathogenic not specified 2017-11-16 criteria provided, single submitter clinical testing Variant summary: The CFTR c.1679+1634A>G variant involves the alteration of a non-conserved intronic nucleotide and 4/5 splice prediction tools predict a significant impact on normal splicing (creation of a novel splicing donor site). cDNA studies proved the aberrant splicing (Chillon_1995). This variant is absent in 30882 control chromosomes (gnomAD). This variant has been reported in many affected individuals. Functional studies showed that individuals with genotype deltaF508/c.1679+1634A>G have only 1%-3% of normal CFTR mRNA. This loss of 97% of normal CFTR mRNA must be responsible for the pancreatic insufficiency and for the severe CF phenotype in these patients (Chillion_1995 and Sosnay_2013). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000046417 SCV000074430 pathogenic Cystic fibrosis 2018-11-30 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the CFTR gene. It does not directly change the encoded amino acid sequence of the CFTR protein. This intronic variant is clearly defined as a Cystic Fibrosis (CF) causative allele (PMID: 23974870, 25122143) and has been reported in many affected individuals. It is also known as c.1679+1.6kbA>G or c.1811+1.6kbA>G in the literature. ClinVar contains an entry for this variant (Variation ID: 53338). Experimental studies have shown that this variant creates a cryptic donor splice site, resulting in the inclusion of a pseudo-exon, and in turn, an altered reading frame in the downstream codons (PMID: 7534040). For these reasons, this variant has been classified as Pathogenic.

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