rs6504112

Positions:

• chr17-62603107-A-C
• chr17-62603107-A-G
• chr17-62603107-A-T

Variant summary

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

The NM_006852.6(TLK2):​c.1859+927A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,946 control chromosomes in the GnomAD database, including 26,761 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 0.59 (26761 hom., cov: 32)
• Consequence: TLK2 NM_006852.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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=-0.86).
• 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.1859+927A>C		intron_variant		ENST00000346027.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLK2	ENST00000346027.10	c.1859+927A>C		intron_variant		1	NM_006852.6	P3

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89670 AN: 151828 Hom.: 26737 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.591 AC: 89733 AN: 151946 Hom.: 26761 Cov.: 32 AF XY: 0.595 AC XY: 44211 AN XY: 74262

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.571

Alfa AF: 0.585 Hom.: 25792

Bravo AF: 0.580

Asia WGS AF: 0.673 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.77

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: rs6504112; hg19: chr17-60680468;