NM_006256.4:c.68C>T

Variant names:

• chr1-88741007-C-T
• rs375306359
• NM_006256.4:c.68C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006256.4(PKN2):​c.68C>T​(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,568,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: PKN2 NM_006256.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031320512).
• BS2: High AC in GnomAd4 at 25 AD gene.

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.68C>T	p.Pro23Leu	missense	Exon 2 of 22	NP_006247.1	Q16513-1
	PKN2	NM_001320709.2		c.68C>T	p.Pro23Leu	missense	Exon 2 of 22	NP_001307638.1	Q16513-2
	PKN2	NM_001320707.2		c.68C>T	p.Pro23Leu	missense	Exon 2 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.68C>T	p.Pro23Leu	missense	Exon 2 of 22	ENSP00000359552.3	Q16513-1
	PKN2	ENST00000370513.9	TSL:1	c.68C>T	p.Pro23Leu	missense	Exon 2 of 21	ENSP00000359544.5	Q16513-3
	PKN2	ENST00000866345.1		c.110C>T	p.Pro37Leu	missense	Exon 3 of 23	ENSP00000536404.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152036 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.0000521 AC: 11 AN: 211330 AF XY: 0.0000347

Gnomad AFR exome AF: 0.000412

Gnomad AMR exome AF: 0.000170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000980

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000311 AC: 44 AN: 1415998 Hom.: 0 Cov.: 30 AF XY: 0.0000242 AC XY: 17 AN XY: 702366

African (AFR) AF: 0.000713 AC: 22 AN: 30834

American (AMR) AF: 0.000396 AC: 13 AN: 32864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39048

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00000548 AC: 6 AN: 1095470

Other (OTH) AF: 0.0000343 AC: 2 AN: 58326

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152036 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 74242

African (AFR) AF: 0.000459 AC: 19 AN: 41420

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00144 AC: 3 AN: 2082

Alfa AF: 0.000117 Hom.: 0

Bravo AF: 0.000344

ESP6500AA AF: 0.000553 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000662 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.59
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.63	N
PhyloP100		2.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.026
Sift	Benign	0.14	T
Sift4G	Benign	0.65	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.28
MPC		0.43
ClinPred		0.042	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.13
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375306359; hg19: chr1-89206690;