rs2230914

Positions:

• chr16-23688738-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005030.6(PLK1):​c.1263C>T​(p.Tyr421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,611,596 control chromosomes in the GnomAD database, including 1,064 homozygotes. 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: 𝑓 0.050 (541 hom., cov: 33)
  • Exomes 𝑓: 0.011 (523 hom.)
• Consequence: PLK1 NM_005030.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

Genes affected

PLK1 (HGNC:9077): (polo like kinase 1) The Ser/Thr protein kinase encoded by this gene belongs to the CDC5/Polo subfamily. It is highly expressed during mitosis and elevated levels are found in many different types of cancer. Depletion of this protein in cancer cells dramatically inhibited cell proliferation and induced apoptosis; hence, it is a target for cancer therapy. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.272 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLK1	NM_005030.6	c.1263C>T	p.Tyr421=	synonymous_variant	7/10	ENST00000300093.9	NP_005021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLK1	ENST00000300093.9	c.1263C>T	p.Tyr421=	synonymous_variant	7/10	1	NM_005030.6	ENSP00000300093	P1
PLK1	ENST00000562272.5	n.3283C>T		non_coding_transcript_exon_variant	6/9	2
PLK1	ENST00000564794.1	n.63C>T		non_coding_transcript_exon_variant	1/4	5
PLK1	ENST00000564947.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7626 AN: 152192 Hom.: 529 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00800

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0166 AC: 4181 AN: 251458 Hom.: 218 AF XY: 0.0135 AC XY: 1835 AN XY: 135898

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.00974

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00573

Gnomad NFE exome AF: 0.00811

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.0112 AC: 16278 AN: 1459286 Hom.: 523 Cov.: 30 AF XY: 0.0103 AC XY: 7513 AN XY: 726152

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00204

Gnomad4 FIN exome AF: 0.00607

Gnomad4 NFE exome AF: 0.00790

Gnomad4 OTH exome AF: 0.0170

GnomAD4 genome AF: 0.0504 AC: 7670 AN: 152310 Hom.: 541 Cov.: 33 AF XY: 0.0494 AC XY: 3678 AN XY: 74488

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.00800

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0267 Hom.: 119

Bravo AF: 0.0558

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.00714

EpiControl AF: 0.00646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2230914; hg19: chr16-23700059;