17-62479268-AGCGGCGGCGGCG-AGCGGCG

Variant names:

• chr17-62479268-AGCGGCG-A
• rs768508482
• NM_006852.6:c.-13_-8delGGCGGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006852.6(TLK2):​c.-13_-8delGGCGGC variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 150,516 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLK2 NM_006852.6 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00014 (21/150516) while in subpopulation AFR AF= 0.00039 (16/40978). AF 95% confidence interval is 0.000244. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLK2	NM_006852.6	c.-13_-8delGGCGGC		splice_region_variant	Exon 1 of 22	ENST00000346027.10	NP_006843.2
TLK2	NM_006852.6	c.-13_-8delGGCGGC		5_prime_UTR_variant	Exon 1 of 22	ENST00000346027.10	NP_006843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLK2	ENST00000346027.10	c.-13_-8delGGCGGC		splice_region_variant	Exon 1 of 22	1	NM_006852.6	ENSP00000275780.7
TLK2	ENST00000346027	c.-13_-8delGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_006852.6	ENSP00000275780.7

Frequencies

GnomAD3 genomes AF: 0.000140 AC: 21 AN: 150516 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000967

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000445

Gnomad OTH AF: 0.000482

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 15940 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 11902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000140 AC: 21 AN: 150516 Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 8 AN XY: 73456

Gnomad4 AFR AF: 0.000390

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000967

Gnomad4 NFE AF: 0.0000445

Gnomad4 OTH AF: 0.000482

Bravo AF: 0.000128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs768508482; hg19: chr17-60556629;