rs786906

Positions:

• chr1-88805891-T-A
• chr1-88805891-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006256.4(PKN2):​c.1677T>A​(p.Ser559Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PKN2 NM_006256.4 missense, splice_region
• Scores: Splicing: ADA: 0.001814
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKN2	NM_006256.4	c.1677T>A	p.Ser559Arg	missense_variant, splice_region_variant	12/22	ENST00000370521.8	NP_006247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKN2	ENST00000370521.8	c.1677T>A	p.Ser559Arg	missense_variant, splice_region_variant	12/22	1	NM_006256.4	ENSP00000359552.3
PKN2	ENST00000370513.9	c.1533T>A	p.Ser511Arg	missense_variant, splice_region_variant	11/21	1		ENSP00000359544.5
PKN2	ENST00000316005.11	c.*81T>A		3_prime_UTR_variant	11/11	5		ENSP00000317851.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.21
Sift	Benign	0.085	T;T
Sift4G	Benign	0.078	T;T
Polyphen		1.0	D;.
Vest4		0.61
MutPred		0.18		Loss of glycosylation at S559 (P = 0.0302);.;
MVP		0.54
MPC		0.76
ClinPred		0.63	D
GERP RS		4.6
Varity_R		0.10
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0018
dbscSNV1_RF	Benign	0.14
SpliceAI score (max)		0.13		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;