chr12-32791112-TA-T

Position:

• chr12-32791112-TA-T

Variant summary

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

The NM_001005242.3(PKP2):​c.*1311del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 148,568 control chromosomes in the GnomAD database, including 1,550 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1550 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PKP2 NM_001005242.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.461

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 12-32791112-TA-T is Benign according to our data. Variant chr12-32791112-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 308470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKP2	NM_001005242.3	c.*1311del		3_prime_UTR_variant	13/13	ENST00000340811.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKP2	ENST00000340811.9	c.*1311del		3_prime_UTR_variant	13/13	1	NM_001005242.3	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15161 AN: 148470 Hom.: 1548 Cov.: 32

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.0854

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.108

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: 0.102 AC: 15168 AN: 148568 Hom.: 1550 Cov.: 32 AF XY: 0.113 AC XY: 8162 AN XY: 72426

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.113

Bravo AF: 0.101

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: rs3833501; hg19: chr12-32944046;