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NM_212472.2(PRKAR1A):c.682C>T (p.Arg228Ter)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 3, 2020
Accession:
VCV000041391.5
Variation ID:
41391
Description:
single nucleotide variant
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NM_212472.2(PRKAR1A):c.682C>T (p.Arg228Ter)

Allele ID
49815
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q24.2
Genomic location
17: 68525886 (GRCh38) GRCh38 UCSC
17: 66522027 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.66522027C>T
NC_000017.11:g.68525886C>T
NM_001276289.1:c.682C>T NP_001263218.1:p.Arg228Ter nonsense
... more HGVS
Protein change
R228*
Other names
-
Canonical SPDI
NC_000017.11:68525885:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA344447
dbSNP: rs281864784
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, single submitter Nov 28, 2019 RCV000034293.4
Pathogenic 1 criteria provided, single submitter Feb 7, 2018 RCV000627207.1
Pathogenic 1 criteria provided, single submitter Nov 3, 2020 RCV001269128.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PRKAR1A - - GRCh38
GRCh37
412 607

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Feb 07, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000748194.3
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R228X nonsense pathogenic variant in the PRKAR1A gene has been reported previously in association with Carney Complex (Kirschner et al., 2000; Horvath et al., … (more)
Pathogenic
(Nov 03, 2020)
criteria provided, single submitter
Method: clinical testing
Carney complex
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001448379.1
Submitted: (Dec 02, 2020)
Evidence details
Publications
PubMed (5)
Comment:
Variant summary: PRKAR1A c.682C>T (p.Arg228X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Pathogenic
(Nov 28, 2019)
criteria provided, single submitter
Method: clinical testing
Carney complex, type 1
Allele origin: germline
Invitae
Accession: SCV001231427.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change creates a premature translational stop signal (p.Arg228*) in the PRKAR1A gene. It is expected to result in an absent or disrupted protein … (more)
pathologic
(Sep 20, 2012)
no assertion criteria provided
Method: curation
Carney Complex
Allele origin: not provided
GeneReviews
Accession: SCV000058239.2
Submitted: (Mar 26, 2013)
Evidence details
Comment:
Converted during submission to Pathogenic.

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Carney Complex Stratakis CA - 2018 PMID: 20301463
Bilateral primary pigmented nodular adrenal disease as a component of Carney syndrome - case report. Sikorska D Endokrynologia Polska 2017 PMID: 28255981
Activation of cyclic AMP signaling leads to different pathway alterations in lesions of the adrenal cortex caused by germline PRKAR1A defects versus those due to somatic GNAS mutations. Almeida MQ The Journal of clinical endocrinology and metabolism 2012 PMID: 22259056
Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype. Libé R The Journal of clinical endocrinology and metabolism 2011 PMID: 21047926
Mutations in regulatory subunit type 1A of cyclic adenosine 5'-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. Bertherat J The Journal of clinical endocrinology and metabolism 2009 PMID: 19293268
Ectopic thymus presenting as a thyroid nodule in a patient with the Carney complex. Courcoutsakis N Thyroid : official journal of the American Thyroid Association 2009 PMID: 19265501
Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Kirschner LS Human molecular genetics 2000 PMID: 11115848

Text-mined citations for rs281864784...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2021