chr17-62613713-G-A

Variant names:

• chr17-62613713-G-A
• rs2245092
• NM_006852.6:c.*1148G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

TLK2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 57

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006852.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLK2	NM_006852.6	MANE Select	c.*1148G>A		3_prime_UTR	Exon 22 of 22	NP_006843.2
	TLK2	NM_001284333.3		c.*1148G>A		3_prime_UTR	Exon 23 of 23	NP_001271262.1	Q86UE8-1
	TLK2	NM_001375269.1		c.*1148G>A		3_prime_UTR	Exon 21 of 21	NP_001362198.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLK2	ENST00000346027.10	TSL:1 MANE Select	c.*1148G>A		3_prime_UTR	Exon 22 of 22	ENSP00000275780.7	Q86UE8-2
	TLK2	ENST00000682085.1		c.*1148G>A		3_prime_UTR	Exon 22 of 22	ENSP00000506744.1	Q86UE8-2
	TLK2	ENST00000902351.1		c.*1148G>A		3_prime_UTR	Exon 22 of 22	ENSP00000572410.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.563 AC: 9 AN: 16

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.583 AC: 24161 AN: 41408

American (AMR) AF: 0.596 AC: 9104 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2118 AN: 3470

East Asian (EAS) AF: 0.824 AC: 4266 AN: 5180

South Asian (SAS) AF: 0.663 AC: 3184 AN: 4800

European-Finnish (FIN) AF: 0.676 AC: 7137 AN: 10550

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44236 AN: 67970

Other (OTH) AF: 0.624 AC: 1320 AN: 2114

Alfa AF: 0.636 Hom.: 3873

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs2245092; hg19: chr17-60691074;