ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.890G>A (p.Arg297Gln) (rs143486492)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000180169 SCV000602982 uncertain significance not specified 2016-12-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000180169 SCV000232561 likely benign not specified 2014-09-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589128 SCV000697053 uncertain significance not provided 2016-11-09 criteria provided, single submitter clinical testing Variant summary: The CFTR c.890G>A (p.Arg297Gln) variant located in the cytoplasmic loop 2 (Choi_2001) causes a missense change involving a conserved nucleotide with 3/5 in silico tools predict a damaging outcome, although a functional study, Seibert_1997, found the variant to act comparable to wild type function. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 59/199236 (1/2021), which does not exceed the estimated maximal expected allele frequency for a pathogenic CFTR variant of 1/77. The variant of interest has been reported in multiple affected individuals with various CFTR-related phenotypes, pancreatitis, asthma, BD, and infertility. In addition, multiple affected individuals were reported to carry another pathogenic CFTR variant in cis with the variant of interest (Graham_1991, Stratakis_2001, and Tzetis_2001), along with a family that indicates the variant did not segregate with disease (Dorval_1995). Although multiple publications have suggested the variant of interest to be causative, multiple clinical diagnostic laboratories with relatively recent evaluations classify the variant as "likely benign/benign." Therefore, until additional information becomes available, the variant of interest has been classified as a "Variant of Uncertain Significance - Possibly Benign."
Invitae RCV000047282 SCV000075295 benign Cystic fibrosis 2016-07-27 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000180169 SCV000710897 likely benign not specified 2017-11-02 criteria provided, single submitter clinical testing p.Arg297Gln variant in exon 8 of CFTR: This variant is not expected to have clin ical significance because it has been identified in 2 unaffected individuals in trans with a pathogenic variant (Dorval 1995). This variant has also been report ed in ClinVar (Variation ID 54082) and has been identified in 0.1% (155/126020) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnoma d.broadinstitute.org; dbSNP rs143486492). Computational prediction tools and con servation analysis suggest that the p.Arg297Gln variant may not impact the prote in, though this information is not predictive enough to rule out pathogenicity. ACMG/AMP Criteria applied: BS2, BP4.

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