chr12-32791224-CA-C

Position:

• chr12-32791224-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001005242.3(PKP2):​c.*1199del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28623 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: PKP2 NM_001005242.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.175

Genes affected

PKP2 (HGNC:9024): (plakophilin 2) This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This gene may regulate the signaling activity of beta-catenin and is required to maintain transcription of genes that control intracellular calcium cycling including ryanodine receptor 2, ankyrin-B, triadin, and calcium channel, voltage-dependent, L type, alpha 1C. Mutations in this gene are associated with different inherited cardiac conditions including Arrythmogenic Cardiomyopathy, Brugada Syndrome, and Idiopathic Ventricular Fibrillation. A processed pseudogene with high similarity to this gene has been mapped to chromosome 12p13. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-32791224-CA-C is Benign according to our data. Variant chr12-32791224-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 308474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKP2	NM_001005242.3	c.*1199del		3_prime_UTR_variant	13/13	ENST00000340811.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKP2	ENST00000340811.9	c.*1199del		3_prime_UTR_variant	13/13	1	NM_001005242.3	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91626 AN: 151376 Hom.: 28606 Cov.: 0

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.602

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.605 AC: 91690 AN: 151494 Hom.: 28623 Cov.: 0 AF XY: 0.598 AC XY: 44240 AN XY: 74014

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.598

Alfa AF: 0.638 Hom.: 3853

Bravo AF: 0.592

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Arrhythmogenic right ventricular cardiomyopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11476598; hg19: chr12-32944158;