GeneBe

rs761636145

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014264.5(PLK4):​c.31-7T>C variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PLK4
NM_014264.5 splice_region, intron

Scores

2
Splicing: ADA: 0.007839
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.557

Publications

0 publications found
Variant links:
Genes affected
PLK4 (HGNC:11397): (polo like kinase 4) This gene encodes a member of the polo family of serine/threonine protein kinases. The protein localizes to centrioles, complex microtubule-based structures found in centrosomes, and regulates centriole duplication during the cell cycle. Three alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Jun 2010]
PLK4 Gene-Disease associations (from GenCC):
  • microcephaly and chorioretinopathy 2
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae)
  • microcephaly and chorioretinopathy 1
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Seckel syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014264.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PLK4
NM_014264.5
MANE Select
c.31-7T>C
splice_region intron
N/ANP_055079.3
PLK4
NM_001441366.1
c.-100T>C
5_prime_UTR
Exon 2 of 16NP_001428295.1
PLK4
NM_001441357.1
c.34-7T>C
splice_region intron
N/ANP_001428286.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PLK4
ENST00000270861.10
TSL:1 MANE Select
c.31-7T>C
splice_region intron
N/AENSP00000270861.5O00444-1
PLK4
ENST00000513090.5
TSL:2
c.31-7T>C
splice_region intron
N/AENSP00000427554.1O00444-2
PLK4
ENST00000852980.1
c.31-7T>C
splice_region intron
N/AENSP00000523039.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1383780
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
693364
African (AFR)
AF:
0.00
AC:
0
AN:
31884
American (AMR)
AF:
0.00
AC:
0
AN:
44612
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25638
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39342
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84652
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53300
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5636
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1041010
Other (OTH)
AF:
0.00
AC:
0
AN:
57706
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
16
DANN
Benign
0.89
PhyloP100
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0078
dbscSNV1_RF
Benign
0.088
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs761636145; hg19: chr4-128802979; API