rs2245092

Positions:

• chr17-62613713-G-A
• chr17-62613713-G-C
• chr17-62613713-G-T

Variant summary

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

The NM_006852.6(TLK2):​c.*1148G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,988 control chromosomes in the GnomAD database, including 30,744 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 0.63 (30741 hom., cov: 31)
  • Exomes 𝑓: 0.50 (3 hom.)
• Consequence: TLK2 NM_006852.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLK2	NM_006852.6	c.*1148G>A		3_prime_UTR_variant	22/22	ENST00000346027.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLK2	ENST00000346027.10	c.*1148G>A		3_prime_UTR_variant	22/22	1	NM_006852.6	P3

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96270 AN: 151850 Hom.: 30716 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.500 AC: 10 AN: 20 Hom.: 3 Cov.: 0 AF XY: 0.563 AC XY: 9 AN XY: 16

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.563

GnomAD4 genome AF: 0.634 AC: 96335 AN: 151968 Hom.: 30741 Cov.: 31 AF XY: 0.638 AC XY: 47379 AN XY: 74280

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.624

Alfa AF: 0.639 Hom.: 3745

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2245092; hg19: chr17-60691074;