chr2-158532879-C-T

Position:

• chr2-158532879-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003628.6(PKP4):​c.-5-301C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 152,254 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.032 (166 hom., cov: 33)
• Consequence: PKP4 NM_003628.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.747

Genes affected

PKP4 (HGNC:9026): (plakophilin 4) Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-158532879-C-T is Benign according to our data. Variant chr2-158532879-C-T is described in ClinVar as [Benign]. Clinvar id is 1290244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKP4	NM_003628.6	c.-5-301C>T		intron_variant		ENST00000389759.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKP4	ENST00000389759.8	c.-5-301C>T		intron_variant		1	NM_003628.6	P3

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4818 AN: 152136 Hom.: 166 Cov.: 33

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0317 AC: 4828 AN: 152254 Hom.: 166 Cov.: 33 AF XY: 0.0319 AC XY: 2373 AN XY: 74440

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0224 Hom.: 9

Bravo AF: 0.0339

Asia WGS AF: 0.0690 AC: 238 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.21

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: rs73966686; hg19: chr2-159389391;