1-88805891-T-C

Variant names:

• chr1-88805891-T-C
• rs786906
• NM_006256.4:c.1677T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Publications: 37 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN2	NM_006256.4	MANE Select	c.1677T>C	p.Ser559Ser	splice_region synonymous	Exon 12 of 22	NP_006247.1	Q16513-1
	PKN2	NM_001320709.2		c.1629T>C	p.Ser543Ser	splice_region synonymous	Exon 12 of 22	NP_001307638.1	Q16513-2
	PKN2	NM_001320707.2		c.1533T>C	p.Ser511Ser	splice_region synonymous	Exon 11 of 21	NP_001307636.1	Q16513-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKN2	ENST00000370521.8	TSL:1 MANE Select	c.1677T>C	p.Ser559Ser	splice_region synonymous	Exon 12 of 22	ENSP00000359552.3	Q16513-1
	PKN2	ENST00000370513.9	TSL:1	c.1533T>C	p.Ser511Ser	splice_region synonymous	Exon 11 of 21	ENSP00000359544.5	Q16513-3
	PKN2	ENST00000866345.1		c.1719T>C	p.Ser573Ser	splice_region synonymous	Exon 13 of 23	ENSP00000536404.1

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

GnomAD2 exomes AF: 0.560 AC: 139468 AN: 249096 AF XY: 0.571

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 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

African (AFR) AF: 0.385 AC: 12872 AN: 33462

American (AMR) AF: 0.515 AC: 22989 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 15756 AN: 26128

East Asian (EAS) AF: 0.472 AC: 18743 AN: 39676

South Asian (SAS) AF: 0.686 AC: 59122 AN: 86210

European-Finnish (FIN) AF: 0.629 AC: 33611 AN: 53412

Middle Eastern (MID) AF: 0.694 AC: 4005 AN: 5768

European-Non Finnish (NFE) AF: 0.547 AC: 607750 AN: 1111682

Other (OTH) AF: 0.556 AC: 33542 AN: 60372

GnomAD4 genome AF: 0.509 AC: 77290 AN: 151992 Hom.: 20351 Cov.: 32 AF XY: 0.517 AC XY: 38416 AN XY: 74288

African (AFR) AF: 0.383 AC: 15881 AN: 41468

American (AMR) AF: 0.501 AC: 7652 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2067 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2405 AN: 5152

South Asian (SAS) AF: 0.683 AC: 3296 AN: 4824

European-Finnish (FIN) AF: 0.630 AC: 6655 AN: 10556

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37643 AN: 67946

Other (OTH) AF: 0.531 AC: 1119 AN: 2108

Alfa AF: 0.533 Hom.: 50104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		4.0
Mutation Taster		=46/54	polymorphism (auto)

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

Other links and lift over

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