rs305217

Positions:

• chr1-88754789-G-A
• chr1-88754789-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006256.4(PKN2):​c.350-5433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,114 control chromosomes in the GnomAD database, including 832 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 0.084 (832 hom., cov: 32)
• Consequence: PKN2 NM_006256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

Genes affected

PKN2 (HGNC:9406): (protein kinase N2) Enables RNA polymerase binding activity; histone deacetylase binding activity; and protein serine/threonine kinase activity. Involved in several processes, including apical junction assembly; positive regulation of cell cycle; and positive regulation of viral genome replication. Located in several cellular components, including cleavage furrow; cytoskeleton; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKN2	NM_006256.4	c.350-5433G>A		intron_variant		ENST00000370521.8	NP_006247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKN2	ENST00000370521.8	c.350-5433G>A		intron_variant		1	NM_006256.4	ENSP00000359552.3
PKN2	ENST00000370513.9	c.350-5433G>A		intron_variant		1		ENSP00000359544.5
PKN2	ENST00000316005.11	c.350-5433G>A		intron_variant		5		ENSP00000317851.7

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12829 AN: 151996 Hom.: 830 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0844 AC: 12837 AN: 152114 Hom.: 832 Cov.: 32 AF XY: 0.0823 AC XY: 6120 AN XY: 74362

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0504 Hom.: 287

Bravo AF: 0.0894

Asia WGS AF: 0.116 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.70

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: rs305217; hg19: chr1-89220472;