ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2856G>C (p.Met952Ile) (rs151048781)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000588974 SCV000696930 pathogenic Congenital bilateral absence of the vas deferens 2016-11-18 criteria provided, single submitter clinical testing Variant summary: The c.2856G>C (p.Met952Ile) in CFTR gene is a missense variant that involves a conserved nucleotide and 3/5 in silico tools predict deleterious outcome. The variant is present in the broad control population dataset of ExAC at a low frequency of 0.00009 (11/121318), which does not exceed the maximum frequency for a pathogenic variant in CFTR gene (1.3%), suggesting this variant is not a common polymorphism. The variant has been reported in multiple CBAVD pts in compound heterozygosity with F508del, R117H, 5T without other clinical manifestations or family history suggestive of CF. Additionally, this variant was reported in at least 2 CF pts. However, it has also been reported in a patient with pancreatic insufficient CF (sweat chloride of 95mEq/L) who had 2 other pathogenic alterations (p.G542X and p.Y914X) in the CFTR gene. Also no functional studies demonstrating an effect of this variant on CFTR activity in-vitro or in-vivo have been reported. Taken together, the variant was classified as Likely Pathogenic for CF-RD (CBAVD) phenotype.
Counsyl RCV000577274 SCV000792125 uncertain significance Cystic fibrosis 2017-06-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733156 SCV000861186 likely pathogenic not provided 2018-05-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000733156 SCV000889301 likely pathogenic not provided 2018-07-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000577274 SCV000916183 likely pathogenic Cystic fibrosis 2017-04-28 criteria provided, single submitter clinical testing The CFTR c.2856G>C (p.Met952Ile) missense variant has been reported in at least six studies and is found in a total of ten individuals with CFTR-related disorders. The p.Met952Ile variant was identified in a compound heterozygous state in five individuals with congenital bilateral absence of the vas deferens (CBAVD), four of whom were identified with the p.Phe508del variant in trans (Uzun et al. 2005; Steiner et al. 2011). The p.Met952Ile was also identified in a heterozygous state in three individuals with cystic fibrosis, one individual with oligospermia, and one individual with CBAVD (Desgeorges et al. 1997; Onay et al. 1998; Gallati et al. 2009; Steiner et al. 2011; Křenková et al. 2013). The p.Met952Ile variant was absent from 415 controls but is reported at a frequency of 0.00012 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the p.Met952Ile variant is classified as likely pathogenic for CFTR-related disorders, and has most commonly been reported in patients with CBAVD. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577274 SCV000679415 not provided Cystic fibrosis no assertion provided literature only

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