rs2711070

Variant names:

• chr2-158646021-G-C
• rs2711070
• NM_003628.6:c.1909+3322G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003628.6(PKP4):​c.1909+3322G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,028 control chromosomes in the GnomAD database, including 16,402 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16402 hom., cov: 33)
• Consequence: PKP4 NM_003628.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP4	NM_003628.6	c.1909+3322G>C		intron_variant	Intron 11 of 21	ENST00000389759.8	NP_003619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP4	ENST00000389759.8	c.1909+3322G>C		intron_variant	Intron 11 of 21	1	NM_003628.6	ENSP00000374409.3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67792 AN: 151910 Hom.: 16384 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.446 AC: 67835 AN: 152028 Hom.: 16402 Cov.: 33 AF XY: 0.450 AC XY: 33425 AN XY: 74292

African (AFR) AF: 0.259 AC: 10730 AN: 41476

American (AMR) AF: 0.584 AC: 8926 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3468

East Asian (EAS) AF: 0.597 AC: 3076 AN: 5154

South Asian (SAS) AF: 0.665 AC: 3206 AN: 4824

European-Finnish (FIN) AF: 0.449 AC: 4735 AN: 10548

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34296 AN: 67954

Other (OTH) AF: 0.438 AC: 923 AN: 2108

Alfa AF: 0.478 Hom.: 2249

Bravo AF: 0.445

Asia WGS AF: 0.585 AC: 2032 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2711070; hg19: chr2-159502533;