Variant 5-58459799-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006622.4(PLK2):c.161C>T(p.Ala54Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLK2
NM_006622.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18120238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLK2	NM_006622.4 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant	1/14	ENST00000274289.8
PLK2	NM_001252226.2 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant, splice_region_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLK2	ENST00000274289.8 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant	1/14	1	NM_006622.4	P1
PLK2	ENST00000617412.1 linkuse as main transcript	c.161C>T	p.Ala54Val	missense_variant, splice_region_variant	1/15	5
PLK2	ENST00000504196.1 linkuse as main transcript	n.288C>T		non_coding_transcript_exon_variant	1/2	2
PLK2	ENST00000514306.1 linkuse as main transcript	n.61C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724740

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.161C>T (p.A54V) alteration is located in exon 1 (coding exon 1) of the PLK2 gene. This alteration results from a C to T substitution at nucleotide position 161, causing the alanine (A) at amino acid position 54 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.61

T;T

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.61

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.41

N;.

REVEL

Benign

0.11

Sift

Benign

0.063

T;.

Sift4G

Benign

0.13

T;T

Polyphen

0.20

B;.

Vest4

0.21

MutPred

0.18

Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);

MVP

0.71

MPC

0.89

ClinPred

0.19

GERP RS

3.4

Varity_R

0.071

gMVP

0.18

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over