ENST00000582809:c.-560C>T

Variant names:

• chr17-62481159-C-T
• rs796730233
• ENST00000582809:c.-560C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000582809(TLK2):​c.-560C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLK2 ENST00000582809 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLK2	NM_006852.6	c.34C>T	p.Arg12Trp	missense_variant	Exon 2 of 22	ENST00000346027.10	NP_006843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLK2	ENST00000346027.10	c.34C>T	p.Arg12Trp	missense_variant	Exon 2 of 22	1	NM_006852.6	ENSP00000275780.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000675 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, autosomal dominant 57 Uncertain:1

Jul 07, 2020

Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.17	.;T;T;.;T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	1.2	.;.;.;L;L;L;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.9	.;.;.;D;D;D;.
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	.;.;.;D;D;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D
Polyphen		0.99, 1.0, 1.0	.;.;.;D;D;D;.
Vest4		0.68, 0.81, 0.81
MutPred		0.45		Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);Loss of disorder (P = 5e-04);
MVP		0.89
MPC		1.6
ClinPred		0.99	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.55

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

Other links and lift over

dbSNP: rs796730233; hg19: chr17-60558520;