ClinVar Miner

Submissions for variant NM_212472.2(PRKAR1A):c.546G>A (p.Thr182=) (rs117639566)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229573 SCV000287681 likely benign Carney complex, type 1 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000229573 SCV000405884 benign Carney complex, type 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000404114 SCV000405885 benign Acrodysostosis 1 with or without hormone resistance 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics RCV000573601 SCV000674433 likely benign Hereditary cancer-predisposing syndrome 2017-03-07 criteria provided, single submitter clinical testing 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.
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.

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