Variant chr1-88771847-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_006256.4(PKN2):c.953A>G(p.Tyr318Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

PKN2
NM_006256.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.744

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKN2	NM_006256.4 linkuse as main transcript	c.953A>G	p.Tyr318Cys	missense_variant	6/22	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.953A>G	p.Tyr318Cys	missense_variant	6/22	1	NM_006256.4	ENSP00000359552.3	Q16513-1
PKN2	ENST00000370513.9 linkuse as main transcript	c.953A>G	p.Tyr318Cys	missense_variant	6/21	1		ENSP00000359544.5	Q16513-3
PKN2	ENST00000316005.11 linkuse as main transcript	c.953A>G	p.Tyr318Cys	missense_variant	6/11	5		ENSP00000317851.7	B1AL79
PKN2	ENST00000436111.1 linkuse as main transcript	c.296A>G	p.Tyr99Cys	missense_variant	2/5	3		ENSP00000401125.1	H0Y5V5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249208

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461426

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ExAC

AF:

0.0000662

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

The c.953A>G (p.Y318C) alteration is located in exon 6 (coding exon 6) of the PKN2 gene. This alteration results from a A to G substitution at nucleotide position 953, causing the tyrosine (Y) at amino acid position 318 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.74

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.017

D;D;D

Sift4G

Uncertain

0.034

D;T;T

Polyphen

0.99

D;D;.

Vest4

0.90

MutPred

0.24

Loss of phosphorylation at Y318 (P = 0.0464);Loss of phosphorylation at Y318 (P = 0.0464);Loss of phosphorylation at Y318 (P = 0.0464);

MVP

0.76

MPC

0.55

ClinPred

0.40

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.45

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over