chr17-62522237-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_006852.6(TLK2):c.187C>T(p.Arg63Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TLK2
NM_006852.6 missense
NM_006852.6 missense
Scores
4
8
2
Clinical Significance
Conservation
PhyloP100: 1.95
Genes affected
TLK2 (HGNC:11842): (tousled like kinase 2) This gene encodes a nuclear serine/threonine kinase that was first identified in Arabidopsis. The encoded protein is thought to function in the regulation of chromatin assembly in the S phase of the cell cycle by regulating the levels of a histone H3/H4 chaperone. This protein is associated with double-strand break repair of DNA damage caused by radiation. Pseudogenes of this gene are present on chromosomes 10 and 17. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, TLK2
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLK2 | NM_006852.6 | c.187C>T | p.Arg63Trp | missense_variant | 4/22 | ENST00000346027.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLK2 | ENST00000346027.10 | c.187C>T | p.Arg63Trp | missense_variant | 4/22 | 1 | NM_006852.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151792Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1
AN:
151792
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460394Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726414
GnomAD4 exome
AF:
AC:
3
AN:
1460394
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726414
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151792Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74122
GnomAD4 genome
?
AF:
AC:
1
AN:
151792
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74122
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2023 | Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0
.;.;D;D;D;.
Vest4
0.72, 0.45, 0.50
MutPred
Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);
MVP
MPC
1.6
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at