rs2108217

Variant names:

• chr2-158590806-C-T
• rs2108217
• NM_003628.6:c.246-12264C>T

Variant summary

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

The NM_003628.6(PKP4):​c.246-12264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 151,962 control chromosomes in the GnomAD database, including 42,618 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 0.74 (42618 hom., cov: 31)
• Consequence: PKP4 NM_003628.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• Publications: 5 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]

LOC105373715 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP4	NM_003628.6	c.246-12264C>T		intron_variant	Intron 3 of 21	ENST00000389759.8	NP_003619.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP4	ENST00000389759.8	c.246-12264C>T		intron_variant	Intron 3 of 21	1	NM_003628.6	ENSP00000374409.3

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112469 AN: 151844 Hom.: 42573 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.741 AC: 112562 AN: 151962 Hom.: 42618 Cov.: 31 AF XY: 0.741 AC XY: 55034 AN XY: 74278

African (AFR) AF: 0.579 AC: 23981 AN: 41440

American (AMR) AF: 0.803 AC: 12263 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3472

East Asian (EAS) AF: 0.920 AC: 4744 AN: 5158

South Asian (SAS) AF: 0.803 AC: 3862 AN: 4812

European-Finnish (FIN) AF: 0.750 AC: 7939 AN: 10582

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 54927 AN: 67920

Other (OTH) AF: 0.740 AC: 1561 AN: 2110

Alfa AF: 0.768 Hom.: 7920

Bravo AF: 0.736

Asia WGS AF: 0.835 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.34
PhyloP100		0.42
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: rs2108217; hg19: chr2-159447318;