17-62479268-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr17-62479268-A-AGCGGCGGCG
• rs768508482
• NM_006852.6:c.-16_-8dupGGCGGCGGC

Variant summary

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

The NM_006852.6(TLK2):​c.-16_-8dupGGCGGCGGC variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 166,558 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00039 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00056 (0 hom.)
• Consequence: TLK2 NM_006852.6 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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 sas. gnomad4 allele frequency = 0.000392 (59/150616) while in subpopulation SAS AF= 0.000834 (4/4798). AF 95% confidence interval is 0.000435. There are 1 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLK2	NM_006852.6	c.-16_-8dupGGCGGCGGC		splice_region_variant	Exon 1 of 22	ENST00000346027.10	NP_006843.2
TLK2	NM_006852.6	c.-16_-8dupGGCGGCGGC		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.-16_-8dupGGCGGCGGC		splice_region_variant	Exon 1 of 22	1	NM_006852.6	ENSP00000275780.7
TLK2	ENST00000346027	c.-16_-8dupGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_006852.6	ENSP00000275780.7

Frequencies

GnomAD3 genomes AF: 0.000392 AC: 59 AN: 150516 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.000387

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000578

Gnomad OTH AF: 0.000964

GnomAD4 exome AF: 0.000565 AC: 9 AN: 15942 Hom.: 0 Cov.: 0 AF XY: 0.000420 AC XY: 5 AN XY: 11904

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: 0.000776

Gnomad4 FIN exome AF: 0.00649

Gnomad4 NFE exome AF: 0.000467

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.000392 AC: 59 AN: 150616 Hom.: 1 Cov.: 31 AF XY: 0.000381 AC XY: 28 AN XY: 73564

Gnomad4 AFR AF: 0.000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000834

Gnomad4 FIN AF: 0.000387

Gnomad4 NFE AF: 0.000579

Gnomad4 OTH AF: 0.000954

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;