NM_002734.5(PRKAR1A):c.286C>T (p.Arg96Ter) AND Carney complex, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000034288.12

Allele description [Variation Report for NM_002734.5(PRKAR1A):c.286C>T (p.Arg96Ter)]

NM_002734.5(PRKAR1A):c.286C>T (p.Arg96Ter)

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_002734.5(PRKAR1A):c.286C>T (p.Arg96Ter)

HGVS:

NC_000017.11:g.68522864C>T
NG_007093.3:g.114242C>T
NM_001276289.2:c.286C>T
NM_001276290.1:c.286C>T
NM_001278433.2:c.286C>T
NM_001369389.1:c.286C>T
NM_001369390.1:c.286C>T
NM_002734.5:c.286C>TMANE SELECT
NM_212471.3:c.286C>T
NM_212472.2:c.286C>T
NP_001263218.1:p.Arg96Ter
NP_001263219.1:p.Arg96Ter
NP_001265362.1:p.Arg96Ter
NP_001356318.1:p.Arg96Ter
NP_001356319.1:p.Arg96Ter
NP_002725.1:p.Arg96Ter
NP_002725.1:p.Arg96Ter
NP_997636.1:p.Arg96Ter
NP_997637.1:p.Arg96Ter
LRG_514t1:c.286C>T
LRG_514t2:c.286C>T
LRG_514:g.114242C>T
LRG_514p1:p.Arg96Ter
LRG_514p2:p.Arg96Ter
NC_000017.10:g.66519005C>T
NM_002734.4:c.286C>T

Protein change:

R96*

Links:

dbSNP: rs281864783

NCBI 1000 Genomes Browser:

rs281864783

Molecular consequence:

NM_001276289.2:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001276290.1:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278433.2:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369389.1:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369390.1:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_002734.5:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_212471.3:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_212472.2:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Carney complex, type 1 (CNC1)
Synonyms:: CARNEY MYXOMA-ENDOCRINE COMPLEX
Identifiers:: MONDO: MONDO:0008057; MedGen: C2607929; Orphanet: 1359; OMIM: 160980

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000287678	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11115848, 19293268, 17396442, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000287678

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 15, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

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, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat L, Libe R, René-Corail F, Stergiopoulos S, Bourdeau I, Bei T, Clauser E, Calender A, Kirschner LS, Bertagna X, Carney JA, Stratakis CA.

J Clin Endocrinol Metab. 2009 Jun;94(6):2085-91. doi: 10.1210/jc.2008-2333. Epub 2009 Mar 17.

PubMed [citation]

PMID:: 19293268
PMCID:: PMC2690418

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000287678.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg96*) in the PRKAR1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRKAR1A are known to be pathogenic (PMID: 11115848, 19293268). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Carney complex (PMID: 17396442). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 41386). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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