5-58456110-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006622.4(PLK2):​c.1300G>A​(p.Ala434Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

PLK2
NM_006622.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05340311).
BS2
High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLK2NM_006622.4 linkuse as main transcriptc.1300G>A p.Ala434Thr missense_variant 10/14 ENST00000274289.8 NP_006613.2 Q9NYY3A0A024QZV1
PLK2NM_001252226.2 linkuse as main transcriptc.1258G>A p.Ala420Thr missense_variant 11/15 NP_001239155.1 Q9NYY3A0A087WUH9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLK2ENST00000274289.8 linkuse as main transcriptc.1300G>A p.Ala434Thr missense_variant 10/141 NM_006622.4 ENSP00000274289.3 Q9NYY3

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152060
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251314
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135810
show subpopulations
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 SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000239
AC:
35
AN:
1461700
Hom.:
0
Cov.:
31
AF XY:
0.0000289
AC XY:
21
AN XY:
727158
show subpopulations
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:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152178
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsNov 08, 2022The c.1300G>A (p.A434T) alteration is located in exon 10 (coding exon 10) of the PLK2 gene. This alteration results from a G to A substitution at nucleotide position 1300, causing the alanine (A) at amino acid position 434 to be replaced by a threonine (T). 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
0.063
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.088
T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.78
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.29
N;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.58
N;.
REVEL
Benign
0.067
Sift
Benign
0.077
T;.
Sift4G
Benign
0.13
T;T
Polyphen
0.0070
B;.
Vest4
0.14
MutPred
0.27
Gain of glycosylation at A434 (P = 0.0073);.;
MVP
0.40
MPC
0.67
ClinPred
0.21
T
GERP RS
5.0
Varity_R
0.061
gMVP
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs552180691; hg19: chr5-57751937; API