Genetic Variant PLK2:c.-197A>G (chr5-58460156-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006622.4(PLK2):c.-197A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 579,132 control chromosomes in the GnomAD database, including 24,897 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 0.32 ( 8615 hom., cov: 33)

Exomes 𝑓: 0.26 ( 16282 hom. )

Consequence

PLK2
NM_006622.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.24

Publications

5 publications found

Variant links:

Genes affected

PLK2 (HGNC:19699): (polo like kinase 2) The protein encoded by this gene is a member of the polo family of serine/threonine protein kinases that have a role in normal cell division. This gene is most abundantly expressed in testis, spleen and fetal tissues, and its expression is inducible by serum, suggesting that it may also play an important role in cells undergoing rapid cell division. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

PLK2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006622.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLK2	NM_006622.4	MANE Select	c.-197A>G		upstream_gene	N/A	NP_006613.2
	PLK2	NM_001252226.2		c.-197A>G		upstream_gene	N/A	NP_001239155.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLK2	ENST00000274289.8	TSL:1 MANE Select	c.-197A>G	upstream_gene	N/A	ENSP00000274289.3
PLK2	ENST00000617412.1	TSL:5	c.-197A>G	upstream_gene	N/A	ENSP00000478685.1
PLK2	ENST00000504196.1	TSL:2	n.-70A>G	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49260

AN:

151886

Hom.:

8599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.264

AC:

112753

AN:

427128

Hom.:

16282

Cov.:

AF XY:

0.260

AC XY:

57960

AN XY:

222712

show subpopulations

African (AFR)

AF:

0.442

AC:

4847

AN:

10958

American (AMR)

AF:

0.280

AC:

4386

AN:

15654

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

2395

AN:

12198

East Asian (EAS)

AF:

0.301

AC:

8304

AN:

27614

South Asian (SAS)

AF:

0.229

AC:

8176

AN:

35688

European-Finnish (FIN)

AF:

0.346

AC:

9305

AN:

26930

Middle Eastern (MID)

AF:

0.243

AC:

427

AN:

1756

European-Non Finnish (NFE)

AF:

0.251

AC:

68316

AN:

272414

Other (OTH)

AF:

0.276

AC:

6597

AN:

23916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

4026

8052

12078

16104

20130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.324

AC:

49313

AN:

152004

Hom.:

8615

Cov.:

AF XY:

0.325

AC XY:

24146

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.457

AC:

18948

AN:

41460

American (AMR)

AF:

0.289

AC:

4424

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

688

AN:

3466

East Asian (EAS)

AF:

0.372

AC:

1907

AN:

5120

South Asian (SAS)

AF:

0.233

AC:

1123

AN:

4820

European-Finnish (FIN)

AF:

0.364

AC:

3858

AN:

10592

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17397

AN:

67932

Other (OTH)

AF:

0.285

AC:

603

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1694

3388

5081

6775

8469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.201

Hom.:

514

Bravo

AF:

0.327

Asia WGS

AF:

0.335

AC:

1165

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.37

(source)

DANN

Benign

0.33

PhyloP100

-3.2

PromoterAI

-0.019

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over