1-88784676-C-T

Variant names:

• chr1-88784676-C-T
• rs201111346
• NM_006256.4:c.1023C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006256.4(PKN2):​c.1023C>T​(p.Ile341Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PKN2 NM_006256.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 3 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=-0.191 with no splicing effect.

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.1023C>T	p.Ile341Ile	synonymous	Exon 7 of 22	NP_006247.1	Q16513-1
	PKN2	NM_001320709.2		c.1023C>T	p.Ile341Ile	synonymous	Exon 7 of 22	NP_001307638.1	Q16513-2
	PKN2	NM_001320707.2		c.1023C>T	p.Ile341Ile	synonymous	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.1023C>T	p.Ile341Ile	synonymous	Exon 7 of 22	ENSP00000359552.3	Q16513-1
	PKN2	ENST00000370513.9	TSL:1	c.1023C>T	p.Ile341Ile	synonymous	Exon 7 of 21	ENSP00000359544.5	Q16513-3
	PKN2	ENST00000866345.1		c.1065C>T	p.Ile355Ile	synonymous	Exon 8 of 23	ENSP00000536404.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000421 AC: 1 AN: 237652 AF XY: 0.00000774

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000914

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447742 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720234

African (AFR) AF: 0.00 AC: 0 AN: 32638

American (AMR) AF: 0.00 AC: 0 AN: 42306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25716

East Asian (EAS) AF: 0.00 AC: 0 AN: 38878

South Asian (SAS) AF: 0.00 AC: 0 AN: 83900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105722

Other (OTH) AF: 0.00 AC: 0 AN: 59732

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.7
DANN	Benign	0.70
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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

dbSNP: rs201111346; hg19: chr1-89250359;