chr1-88787674-A-G

Variant names:

• chr1-88787674-A-G
• rs786908
• NM_006256.4:c.1281+1461A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 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.1281+1461A>G		intron	N/A	NP_006247.1
	PKN2	NM_001320709.2		c.1233+1461A>G		intron	N/A	NP_001307638.1
	PKN2	NM_001320707.2		c.1281+1461A>G		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.1281+1461A>G		intron	N/A	ENSP00000359552.3
	PKN2	ENST00000370513.9	TSL:1	c.1281+1461A>G		intron	N/A	ENSP00000359544.5
	PKN2	ENST00000316005.11	TSL:5	c.1281+1461A>G		intron	N/A	ENSP00000317851.7

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

African (AFR) AF: 0.925 AC: 38463 AN: 41568

American (AMR) AF: 0.625 AC: 9555 AN: 15294

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

East Asian (EAS) AF: 0.644 AC: 3334 AN: 5174

South Asian (SAS) AF: 0.814 AC: 3921 AN: 4816

European-Finnish (FIN) AF: 0.735 AC: 7786 AN: 10590

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42904 AN: 67946

Other (OTH) AF: 0.708 AC: 1497 AN: 2114

Alfa AF: 0.692 Hom.: 4845

Bravo AF: 0.719

Asia WGS AF: 0.758 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.5
DANN	Benign	0.69
PhyloP100		-0.069
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: rs786908; hg19: chr1-89253357;