ClinVar Miner

Submissions for variant NM_002734.4(PRKAR1A):c.546G>A (p.Thr182=) (rs117639566)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573601 SCV000674433 likely benign Hereditary cancer-predisposing syndrome 2017-03-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
GeneDx RCV000610412 SCV000715898 likely benign not specified 2017-02-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000348778 SCV000405884 likely benign Carney complex 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000404114 SCV000405885 likely benign Acrodysostosis 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000610412 SCV000920084 benign not specified 2018-03-05 criteria provided, single submitter clinical testing Variant summary: PRKAR1A c.546G>A alters a conserved nucleotide resulting in a synonymous change and 5/5 in silico tools predict no significant effect on splicing. However, these predictions have yet to be functionally assessed. The variant allele was found at a frequency of 9.8e-05 in 245944 control chromosomes (gnomAD). The observed variant frequency is approximately 52 fold above the estimated maximal expected allele frequency for a pathogenic variant in PRKAR1A causing Carney Complex phenotype (1.9e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.546G>A in individuals affected with Carney Complex and no experimental evidence demonstrating its impact on protein function have been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as "likely benign." Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000229573 SCV000287681 likely benign Carney complex, type 1 2017-10-30 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.