Variant 1-88805891-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_006256.4(PKN2):c.1677T>C(p.Ser559Ser) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.549 in 1,613,366 control chromosomes in the GnomAD database, including 246,194 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20351 hom., cov: 32)

Exomes 𝑓: 0.55 ( 225843 hom. )

Consequence

PKN2
NM_006256.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00009795

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96

Variant links:

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]

PKN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKN2	NM_006256.4 linkuse as main transcript	c.1677T>C	p.Ser559Ser	splice_region_variant, synonymous_variant	12/22	ENST00000370521.8	NP_006247.1	Q16513-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PKN2	ENST00000370521.8 linkuse as main transcript	c.1677T>C	p.Ser559Ser	splice_region_variant, synonymous_variant	12/22	1	NM_006256.4	ENSP00000359552.3	Q16513-1
PKN2	ENST00000370513.9 linkuse as main transcript	c.1533T>C	p.Ser511Ser	splice_region_variant, synonymous_variant	11/21	1		ENSP00000359544.5	Q16513-3
PKN2	ENST00000316005.11 linkuse as main transcript	c.*81T>C		3_prime_UTR_variant	11/11	5		ENSP00000317851.7	B1AL79

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77288

AN:

151874

Hom.:

20358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.532

GnomAD3 exomes

AF:

0.560

AC:

139468

AN:

249096

Hom.:

39947

AF XY:

0.571

AC XY:

77128

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.465

Gnomad SAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.631

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.576

GnomAD4 exome

AF:

0.553

AC:

808390

AN:

1461374

Hom.:

225843

Cov.:

AF XY:

0.558

AC XY:

405460

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.603

Gnomad4 EAS exome

AF:

0.472

Gnomad4 SAS exome

AF:

0.686

Gnomad4 FIN exome

AF:

0.629

Gnomad4 NFE exome

AF:

0.547

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.509

AC:

77290

AN:

151992

Hom.:

20351

Cov.:

AF XY:

0.517

AC XY:

38416

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.683

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.531

Alfa

AF:

0.539

Hom.:

35146

Bravo

AF:

0.489

Asia WGS

AF:

0.542

AC:

1885

AN:

3478

EpiCase

AF:

0.550

EpiControl

AF:

0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000098

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over