rs10489889

Variant names:

• chr1-88749122-G-A
• rs10489889
• NM_006256.4:c.349+7834G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-88749122-G-A
• chr1-88749122-G-C

Variant summary

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

The NM_006256.4(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 NM_006256.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006256.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN2	NM_006256.4	MANE Select	c.349+7834G>A		intron	N/A	NP_006247.1
	PKN2	NM_001320709.2		c.349+7834G>A		intron	N/A	NP_001307638.1
	PKN2	NM_001320707.2		c.349+7834G>A		intron	N/A	NP_001307636.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN2	ENST00000370521.8	TSL:1 MANE Select	c.349+7834G>A		intron	N/A	ENSP00000359552.3
	PKN2	ENST00000370513.9	TSL:1	c.349+7834G>A		intron	N/A	ENSP00000359544.5
	PKN2	ENST00000866345.1		c.391+7834G>A		intron	N/A	ENSP00000536404.1

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

African (AFR) AF: 0.176 AC: 7314 AN: 41442

American (AMR) AF: 0.0259 AC: 395 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0179 AC: 86 AN: 4814

European-Finnish (FIN) AF: 0.0670 AC: 710 AN: 10596

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0202 AC: 1376 AN: 68004

Other (OTH) AF: 0.0535 AC: 113 AN: 2112

Alfa AF: 0.0323 Hom.: 90

Bravo AF: 0.0681

Asia WGS AF: 0.0290 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.41
PhyloP100		-0.041
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: rs10489889; hg19: chr1-89214805;