NM_212472.2(PRKAR1A):c.891+3A>G AND Carney complex, type 1

Clinical significance:Likely pathogenic (Last evaluated: Mar 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000013500.26

Allele description [Variation Report for NM_212472.2(PRKAR1A):c.891+3A>G]

NM_212472.2(PRKAR1A):c.891+3A>G

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.891+3A>G
HGVS:
  • NC_000017.11:g.68528994A>G
  • NG_007093.3:g.120372A>G
  • NM_001276289.1:c.891+3A>G
  • NM_001276290.1:c.891+3A>G
  • NM_001278433.1:c.891+3A>G
  • NM_001369389.1:c.891+3A>G
  • NM_001369390.1:c.891+3A>G
  • NM_002734.4:c.891+3A>G
  • NM_212471.2:c.891+3A>G
  • NM_212472.2:c.891+3A>G
  • LRG_514t1:c.891+3A>G
  • LRG_514t2:c.891+3A>G
  • LRG_514:g.120372A>G
  • NC_000017.10:g.66525135A>G
  • NM_212472.1:c.891+3A>G
Nucleotide change:
IVS8DS, A-G, +3
Links:
OMIM: 188830.0003; dbSNP: rs281864799
NCBI 1000 Genomes Browser:
rs281864799
Molecular consequence:
  • NM_001276289.1:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001276290.1:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001278433.1:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369389.1:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001369390.1:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_002734.4:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_212471.2:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_212472.2:c.891+3A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000033747OMIMno assertion criteria providedPathogenic
(Sep 1, 2000)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000058248GeneReviewsno assertion criteria providedpathologic
(Sep 20, 2012)
not providedcuration

SCV001576383Invitaecriteria provided, single submitter
Likely pathogenic
(Mar 24, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providednot providednot providednot providednot providednot providednot providednot providedcuration

Citations

PubMed

Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new association.

Gaujoux S, Tissier F, Ragazzon B, Rebours V, Saloustros E, Perlemoine K, Vincent-Dejean C, Meurette G, Cassagnau E, Dousset B, Bertagna X, Horvath A, Terris B, Carney JA, Stratakis CA, Bertherat J.

J Clin Endocrinol Metab. 2011 Nov;96(11):E1888-95. doi: 10.1210/jc.2011-1433. Epub 2011 Sep 7.

PubMed [citation]
PMID:
21900385
PMCID:
PMC3205895

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000033747.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In affected members of a family with Carney complex (CNC1; 160980), Kirschner et al. (2000) identified a heterozygous A-to-G transition at position +3 of intron 8 of the PRKAR1A gene, presumably resulting in a defect in splicing of the protein product.

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

From GeneReviews, SCV000058248.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

From Invitae, SCV001576383.1

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

Description

This sequence change falls in intron 9 of the PRKAR1A gene. It does not directly change the encoded amino acid sequence of the PRKAR1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Carney complex (PMID: 10973256, 21900385, Invitae). ClinVar contains an entry for this variant (Variation ID: 12664). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 10973256). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: May 14, 2021

Support Center