chr1-88784770-A-C

Variant names:

• chr1-88784770-A-C
• NM_006256.4:c.1117A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006256.4(PKN2):​c.1117A>C​(p.Ser373Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PKN2 NM_006256.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23742765).

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.1117A>C	p.Ser373Arg	missense	Exon 7 of 22	NP_006247.1	Q16513-1
	PKN2	NM_001320709.2		c.1117A>C	p.Ser373Arg	missense	Exon 7 of 22	NP_001307638.1	Q16513-2
	PKN2	NM_001320707.2		c.1117A>C	p.Ser373Arg	missense	Exon 7 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.1117A>C	p.Ser373Arg	missense	Exon 7 of 22	ENSP00000359552.3	Q16513-1
	PKN2	ENST00000370513.9	TSL:1	c.1117A>C	p.Ser373Arg	missense	Exon 7 of 21	ENSP00000359544.5	Q16513-3
	PKN2	ENST00000866345.1		c.1159A>C	p.Ser387Arg	missense	Exon 8 of 23	ENSP00000536404.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	0.95
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Benign	0.15	T
Sift4G	Benign	0.087	T
Polyphen		0.50	P
Vest4		0.38
MutPred		0.17		Loss of phosphorylation at S373 (P = 0.0029)
MVP		0.36
MPC		0.49
ClinPred		0.68	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.46
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr1-89250453;