rs27770

Variant names:

• chr16-23690217-A-G
• rs27770
• NM_005030.6:c.*154A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-23690217-A-G
• chr16-23690217-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005030.6(PLK1):​c.*154A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 649,526 control chromosomes in the GnomAD database, including 17,202 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 0.20 (3233 hom., cov: 32)
  • Exomes 𝑓: 0.23 (13969 hom.)
• Consequence: PLK1 NM_005030.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 29 publications found

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]

ERN2 (HGNC:16942): (endoplasmic reticulum to nucleus signaling 2) Enables several functions, including ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including apoptotic chromosome condensation; negative regulation of transcription, DNA-templated; and rRNA catabolic process. Predicted to be located in endoplasmic reticulum membrane and endoplasmic reticulum quality control compartment. Predicted to be integral component of membrane. Predicted to be part of IRE1-TRAF2-ASK1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLK1	NM_005030.6	c.*154A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000300093.9	NP_005021.2
ERN2	NM_033266.4	c.*614T>C		downstream_gene_variant		ENST00000256797.9	NP_150296.4
ERN2	NM_001308220.2	c.*614T>C		downstream_gene_variant			NP_001295149.2
ERN2	XM_047433506.1	c.*614T>C		downstream_gene_variant			XP_047289462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLK1	ENST00000300093.9	c.*154A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_005030.6	ENSP00000300093.4
ERN2	ENST00000256797.9	c.*614T>C		downstream_gene_variant		1	NM_033266.4	ENSP00000256797.5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29877 AN: 151972 Hom.: 3236 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.232 AC: 24425 AN: 105350 AF XY: 0.234

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.442

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.226 AC: 112483 AN: 497436 Hom.: 13969 Cov.: 5 AF XY: 0.228 AC XY: 60190 AN XY: 264204

African (AFR) AF: 0.126 AC: 1795 AN: 14224

American (AMR) AF: 0.174 AC: 4348 AN: 25040

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 2619 AN: 15026

East Asian (EAS) AF: 0.436 AC: 14361 AN: 32938

South Asian (SAS) AF: 0.246 AC: 12547 AN: 51102

European-Finnish (FIN) AF: 0.259 AC: 8257 AN: 31860

Middle Eastern (MID) AF: 0.187 AC: 696 AN: 3714

European-Non Finnish (NFE) AF: 0.209 AC: 61669 AN: 295414

Other (OTH) AF: 0.220 AC: 6191 AN: 28118

GnomAD4 genome AF: 0.197 AC: 29888 AN: 152090 Hom.: 3233 Cov.: 32 AF XY: 0.200 AC XY: 14902 AN XY: 74346

African (AFR) AF: 0.127 AC: 5282 AN: 41494

American (AMR) AF: 0.178 AC: 2722 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2231 AN: 5156

South Asian (SAS) AF: 0.260 AC: 1255 AN: 4818

European-Finnish (FIN) AF: 0.274 AC: 2900 AN: 10566

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14218 AN: 67966

Other (OTH) AF: 0.211 AC: 446 AN: 2114

Alfa AF: 0.194 Hom.: 646

Bravo AF: 0.187

Asia WGS AF: 0.291 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.83
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs27770; hg19: chr16-23701538; COSMIC: COSV107219628; COSMIC: COSV107219628;