rs12451705

chr17-62579973-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006852.6(TLK2):c.1287-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 608,284 control chromosomes in the GnomAD database, including 83,953 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (16821 hom., cov: 32)
  • Exomes 𝑓: 0.53 (67132 hom.)
• Consequence: TLK2 NM_006852.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLK2	NM_006852.6	c.1287-138C>T		intron_variant		ENST00000346027.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLK2	ENST00000346027.10	c.1287-138C>T		intron_variant		1	NM_006852.6	P3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64762 AN: 151876 Hom.: 16822 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.533 AC: 243031 AN: 456288 Hom.: 67132 AF XY: 0.530 AC XY: 127391 AN XY: 240142

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.664

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.426 AC: 64764 AN: 151996 Hom.: 16821 Cov.: 32 AF XY: 0.432 AC XY: 32094 AN XY: 74278

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.441

Alfa AF: 0.516 Hom.: 14030

Bravo AF: 0.402

Asia WGS AF: 0.485 AC: 1689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.0
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12451705; hg19: chr17-60657334;