Variant chr12-32821311-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001407157.1(PKP2):c.2190G>A(p.Leu730Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,517,982 control chromosomes in the GnomAD database, including 460,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41590 hom., cov: 32)

Exomes 𝑓: 0.78 ( 418743 hom. )

Consequence

PKP2
NM_001407157.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.697

Variant links:

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]

PKP2 links:

PKP2 (HGNC:):

PKP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-32821311-C-T is Benign according to our data. Variant chr12-32821311-C-T is described in ClinVar as [Benign]. Clinvar id is 259441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-32821311-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.697 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP2	NM_001005242.3 linkuse as main transcript	c.2013+45G>A		intron_variant		ENST00000340811.9	NP_001005242.2	Q99959-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP2	ENST00000340811.9 linkuse as main transcript	c.2013+45G>A		intron_variant		1	NM_001005242.3	ENSP00000342800.5		Q99959-2

Frequencies

GnomAD3 genomes

AF:

0.731

AC:

111059

AN:

151952

Hom.:

41566

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.782

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.815

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.819

Gnomad OTH

AF:

0.732

GnomAD3 exomes

AF:

0.703

AC:

175020

AN:

248858

Hom.:

64300

AF XY:

0.711

AC XY:

95728

AN XY:

134600

show subpopulations

Gnomad AFR exome

AF:

0.656

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.350

Gnomad SAS exome

AF:

0.608

Gnomad FIN exome

AF:

0.814

Gnomad NFE exome

AF:

0.817

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.775

AC:

1058965

AN:

1365912

Hom.:

418743

Cov.:

AF XY:

0.772

AC XY:

529563

AN XY:

685698

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.540

Gnomad4 ASJ exome

AF:

0.785

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.608

Gnomad4 FIN exome

AF:

0.812

Gnomad4 NFE exome

AF:

0.818

Gnomad4 OTH exome

AF:

0.760

GnomAD4 genome

AF:

0.731

AC:

111126

AN:

152070

Hom.:

41590

Cov.:

AF XY:

0.724

AC XY:

53800

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.664

Gnomad4 AMR

AF:

0.624

Gnomad4 ASJ

AF:

0.782

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.596

Gnomad4 FIN

AF:

0.815

Gnomad4 NFE

AF:

0.819

Gnomad4 OTH

AF:

0.726

Alfa

AF:

0.793

Hom.:

82592

Bravo

AF:

0.714

Asia WGS

AF:

0.473

AC:

1647

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Arrhythmogenic right ventricular dysplasia 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.3

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over