chr1-88749122-G-A

Position:

• chr1-88749122-G-A

Variant summary

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

The ENST00000370521.8(PKN2):​c.349+7834G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,090 control chromosomes in the GnomAD database, including 690 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 0.067 (690 hom., cov: 31)
• Consequence: PKN2 ENST00000370521.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKN2	NM_006256.4	c.349+7834G>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.349+7834G>A		intron_variant		1	NM_006256.4	ENSP00000359552	P1
PKN2	ENST00000370513.9	c.349+7834G>A		intron_variant		1		ENSP00000359544
PKN2	ENST00000316005.11	c.349+7834G>A		intron_variant		5		ENSP00000317851

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10124 AN: 151972 Hom.: 685 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0668 AC: 10166 AN: 152090 Hom.: 690 Cov.: 31 AF XY: 0.0679 AC XY: 5052 AN XY: 74368

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0202

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0258 Hom.: 51

Bravo AF: 0.0681

Asia WGS AF: 0.0290 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.41

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: rs10489889; hg19: chr1-89214805;