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NM_001005242.3(PKP2):c.1170+4_1170+7del AND Arrhythmogenic right ventricular dysplasia 9

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 28, 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:
RCV001212172.6

Allele description [Variation Report for NM_001005242.3(PKP2):c.1170+4_1170+7del]

NM_001005242.3(PKP2):c.1170+4_1170+7del

Gene:
PKP2:plakophilin 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12p11.21
Genomic location:
Preferred name:
NM_001005242.3(PKP2):c.1170+4_1170+7del
HGVS:
  • NC_000012.11:g.33021854_33021857del
  • NC_000012.12:g.32868923_32868926del
  • NG_009000.1:g.32924_32927del
  • NM_001005242.3:c.1170+4_1170+7delMANE SELECT
  • NM_004572.4:c.1170+4_1170+7del
  • LRG_398t1:c.1170+4_1170+7del
  • LRG_398:g.32924_32927del
  • NC_000012.11:g.33021854_33021857del
  • NC_000012.11:g.33021854_33021857delCACT
  • NC_000012.11:g.33021857_33021860del
  • NM_004572.3:c.1170+4_1170+7del
  • NM_004572.3:c.1170+4_1170+7delAGTG
  • c.1170+4_1170+7delAGTG
Links:
dbSNP: rs397516988
NCBI 1000 Genomes Browser:
rs397516988
Molecular consequence:
  • NM_001005242.3:c.1170+4_1170+7del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004572.4:c.1170+4_1170+7del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Arrhythmogenic right ventricular dysplasia 9 (ARVD9)
Synonyms:
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 9; Arrhythmogenic right ventricular cardiomyopathy, type 9; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 9
Identifiers:
MONDO: MONDO:0012180; MedGen: C1836906; OMIM: 609040

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001383748Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Dec 28, 2023)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmosomal Variants Are Rarely De Novo.

van Lint FHM, Murray B, Tichnell C, Zwart R, Amat N, Lekanne Deprez RH, Dittmann S, Stallmeyer B, Calkins H, van der Smagt JJ, van den Wijngaard A, Dooijes D, van der Zwaag PA, Schulze-Bahr E, Judge DP, Jongbloed JDH, van Tintelen JP, James CA.

Circ Genom Precis Med. 2019 Aug;12(8):e002467. doi: 10.1161/CIRCGEN.119.002467. Epub 2019 Aug 6.

PubMed [citation]
PMID:
31386562

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001383748.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change falls in intron 4 of the PKP2 gene. It does not directly change the encoded amino acid sequence of the PKP2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs397516988, gnomAD 0.007%). This variant has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 31386562). ClinVar contains an entry for this variant (Variation ID: 45012). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 26, 2024