rs786908

chr1-88787674-A-G

Variant summary

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

The NM_006256.4(PKN2):c.1281+1461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,180 control chromosomes in the GnomAD database, including 41,486 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 0.73 (41486 hom., cov: 32)
• Consequence: PKN2 NM_006256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKN2	NM_006256.4	c.1281+1461A>G		intron_variant		ENST00000370521.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKN2	ENST00000370521.8	c.1281+1461A>G		intron_variant		1	NM_006256.4	P1
PKN2	ENST00000370513.9	c.1281+1461A>G		intron_variant		1
PKN2	ENST00000316005.11	c.1281+1461A>G		intron_variant		5
PKN2	ENST00000436111.1	c.439+1461A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110418 AN: 152062 Hom.: 41438 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.726 AC: 110515 AN: 152180 Hom.: 41486 Cov.: 32 AF XY: 0.733 AC XY: 54514 AN XY: 74396

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.708

Alfa AF: 0.683 Hom.: 4515

Bravo AF: 0.719

Asia WGS AF: 0.758 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	4.5
Dann	Benign	0.69

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: rs786908; hg19: chr1-89253357;