ClinVar Miner

Submissions for variant NM_212472.2(PRKAR1A):c.678C>T (p.Ile226=) (rs200592054)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000299630 SCV000405886 benign Acrodysostosis 1 with or without hormone resistance 2018-01-12 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 RCV001082572 SCV000405887 benign Carney complex, type 1 2018-01-12 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.
Invitae RCV001082572 SCV000556799 benign Carney complex, type 1 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000566997 SCV000674435 benign Hereditary cancer-predisposing syndrome 2017-04-20 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Synonymous alterations with insufficient evidence to classify as benign;In silico models in agreement (benign)
Integrated Genetics/Laboratory Corporation of America RCV000589555 SCV000698032 benign not provided 2017-02-23 criteria provided, single submitter clinical testing Variant summary: The PRKAR1A c.678C>T (p.Ile226Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide, which 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts alterations to ESE binding. However, these predictions have yet to be confirmed by functional studies. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 87/121124, predominantly observed in the East Asian subpopulation at a frequency of 0.009961 (86/8634). This frequency is about 5313 times the estimated maximal expected allele frequency of a pathogenic PRKAR1A variant (0.0000019), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, a clinical diagnostic laboratory classifies the variant as "likely benign." The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign.

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