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

Clinical significance:Pathogenic (Last evaluated: Nov 3, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001269128.1

Allele description [Variation Report for NM_212472.2(PRKAR1A):c.682C>T (p.Arg228Ter)]

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

Gene:
PRKAR1A:protein kinase cAMP-dependent type I regulatory subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q24.2
Genomic location:
Preferred name:
NM_212472.2(PRKAR1A):c.682C>T (p.Arg228Ter)
HGVS:
  • NC_000017.11:g.68525886C>T
  • NG_007093.3:g.117264C>T
  • NM_001276289.1:c.682C>T
  • NM_001276290.1:c.682C>T
  • NM_001278433.1:c.682C>T
  • NM_001369389.1:c.682C>T
  • NM_001369390.1:c.682C>T
  • NM_002734.4:c.682C>T
  • NM_212471.2:c.682C>T
  • NM_212472.2:c.682C>T
  • NP_001263218.1:p.Arg228Ter
  • NP_001263219.1:p.Arg228Ter
  • NP_001265362.1:p.Arg228Ter
  • NP_001356318.1:p.Arg228Ter
  • NP_001356319.1:p.Arg228Ter
  • NP_002725.1:p.Arg228Ter
  • NP_997636.1:p.Arg228Ter
  • NP_997637.1:p.Arg228Ter
  • LRG_514t1:c.682C>T
  • LRG_514t2:c.682C>T
  • LRG_514:g.117264C>T
  • LRG_514p1:p.Arg228Ter
  • LRG_514p2:p.Arg228Ter
  • NC_000017.10:g.66522027C>T
  • NM_002734.3:c.682C>T
  • NM_212472.1:c.682C>T
Protein change:
R228*
Links:
dbSNP: rs281864784
NCBI 1000 Genomes Browser:
rs281864784
Molecular consequence:
  • NM_001276289.1:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001276290.1:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001278433.1:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369389.1:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001369390.1:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_002734.4:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_212471.2:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_212472.2:c.682C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Carney complex
Synonyms:
Carney syndrome; Carney myxoma-endocrine complex; Myxoma, spotty pigmentation, and endocrine overactivity
Identifiers:
MONDO: MONDO:0015285; MedGen: C0406810

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001448379Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Nov 3, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex.

Kirschner LS, Sandrini F, Monbo J, Lin JP, Carney JA, Stratakis CA.

Hum Mol Genet. 2000 Dec 12;9(20):3037-46.

PubMed [citation]
PMID:
11115848

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, Azevedo MF, Xekouki P, Bimpaki EI, Horvath A, Collins MT, Karaviti LP, Jeha GS, Bhattacharyya N, Cheadle C, Watkins T, Bourdeau I, Nesterova M, Stratakis CA.

J Clin Endocrinol Metab. 2012 Apr;97(4):E687-93. doi: 10.1210/jc.2011-3000. Epub 2012 Jan 18.

PubMed [citation]
PMID:
22259056
PMCID:
PMC3319183
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001448379.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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 due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251178 control chromosomes (gnomAD). c.682C>T has been reported in the literature in individuals affected with Carney Complex (Kirschner_2000, Courcoutsakis_2009, Libe_2010, Sikorska_2017). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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