1-88805891-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006256.4(PKN2):c.1677T>C(p.Ser559=) 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

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 -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	UniProt
PKN2	NM_006256.4	c.1677T>C	p.Ser559=	splice_region_variant, synonymous_variant	12/22	ENST00000370521.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKN2	ENST00000370521.8	c.1677T>C	p.Ser559=	splice_region_variant, synonymous_variant	12/22	1	NM_006256.4	P1
PKN2	ENST00000370513.9	c.1533T>C	p.Ser511=	splice_region_variant, synonymous_variant	11/21	1
PKN2	ENST00000316005.11	c.*81T>C		3_prime_UTR_variant	11/11	5

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77288 AN: 151874 Hom.: 20358 Cov.: 32

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

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.: 44 AF XY: 0.558 AC XY: 405460 AN XY: 727016

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.: 32 AF XY: 0.517 AC XY: 38416 AN XY: 74288

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	14
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

Other links and lift over

dbSNP: rs786906; hg19: chr1-89271574; COSMIC: COSV60134042; COSMIC: COSV60134042;