ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2476G>A (p.Glu826Lys) (rs397508381)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000577037 SCV000795535 uncertain significance Cystic fibrosis 2017-11-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781228 SCV000919132 uncertain significance not specified 2018-08-06 criteria provided, single submitter clinical testing Variant summary: CFTR c.2476G>A (p.Glu826Lys) results in a conservative amino acid change located in the CFTR regulator domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.1e-05 in 188924 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant has been reported in the literature in control individuals (Morea 2005, Tzetis 2007), in a CF patient (Prontera 2016), and in a sarcoidosis patient (Bombieri 1998). These reports do not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. The variant was also found in a CBAVD patient who carried the pathogenic c.5T_TG12 variant in cis and an unspecified CF-causing variant in trans (Claustres 2017, CFTR-France database), providing supporting evidence for a benign role. While the variant did not affect the protein maturation, it was reported to result in a slightly lower open channel probability, however single channel conductances were not different from the wild-type (Wei 1998, Vankeerberghen 1998). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577037 SCV000678990 not provided Cystic fibrosis no assertion provided literature only

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