ClinVar Miner

Submissions for variant NM_212472.2(PRKAR1A):c.489T>C (p.Thr163=) (rs143672551)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456278 SCV000556797 benign Carney complex, type 1 2020-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000567376 SCV000674432 likely benign Hereditary cancer-predisposing syndrome 2017-06-21 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
GeneDx RCV000601259 SCV000715739 likely benign not specified 2017-02-06 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000601259 SCV001362691 benign not specified 2019-02-01 criteria provided, single submitter clinical testing Variant summary: PRKAR1A c.489T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00031 in 282814 control chromosomes in the gnomAD database, predominantly within the African subpopulation at a frequency of 0.0034. The observed variant frequency within African control individuals in the gnomAD database is approximately 1800 fold of 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 a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.489T>C in individuals affected with Carney Complex and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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