chr1-88805891-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006256.4(PKN2):​c.1677T>G​(p.Ser559Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000116 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PKN2 NM_006256.4 missense, splice_region
• Scores: Splicing: ADA: 0.0008061
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKN2	NM_006256.4	c.1677T>G	p.Ser559Arg	missense_variant, splice_region_variant	Exon 12 of 22	ENST00000370521.8	NP_006247.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461674 Hom.: 0 Cov.: 44 AF XY: 0.0000138 AC XY: 10 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.040	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		4.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.19
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		0.55	D
GERP RS		4.6
Varity_R		0.10
gMVP		0.36
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00081
dbscSNV1_RF	Benign	0.16
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

Other links and lift over

dbSNP: rs786906; hg19: chr1-89271574;