ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2052delA (rs121908746)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
American College of Medical Genetics and Genomics (ACMG) RCV000043563 SCV000071399 pathogenic Cystic fibrosis 2004-03-03 practice guideline curation Converted during submission to Pathogenic.
CFTR2 RCV000043563 SCV000071472 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000043563 SCV000485160 pathogenic Cystic fibrosis 2016-02-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000043563 SCV000696884 pathogenic Cystic fibrosis 2016-01-25 criteria provided, single submitter clinical testing Variant summary: This c.2052delA variant causes a frameshift, which alters the proteins amino acid sequence beginning at position 684 and leads to a premature termination codon 38 amino acids downstream. It is predicted to cause a truncated or absent CFTR protein. Loss-of-function due to mutations in this gene is an established disease mechanism in CF or CFTR-RD. This variant was found in 7/119584 chromosomes from broad and large populations of ExAC at a frequency of 0.0000585, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0129603) in this gene. This variant is widely reported as a common CF-causing variant in literature and databases. The variant has been found in patients with classic CF. Multiple clinical labs/reputable databases call this variant as pathogenic. Taken together, this variant has been classified as a Pathogenic.
GeneDx RCV000598782 SCV000709944 pathogenic not provided 2017-07-31 criteria provided, single submitter clinical testing The c.2052delA pathogenic variant in the CFTR gene has been reported previously, sometimes using alternate nomenclature (2184delA), either in the homozygous state or in trans with another CFTR variant in multiple individuals with cystic fibrosis (Lissens et al., 1993; Dork et al., 1994; Jung et al., 2011). The c.2052delA variant causes a frameshift starting with codon Lysine 684, changes this amino acid to an Asparagine residue, and creates a premature Stop codon at position 38 of the new reading frame, denoted p.Lys684AsnfsX38. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2052delA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.2052delA as a pathogenic variant.

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