rs768508482

Variant names:

• chr17-62479267-GAGCGGCGGCGGC-GA
• NM_006852.6:c.-26_-16delCGGCGGCGGCG

Your query was ambiguous. Multiple possible variants found:

• chr17-62479268-AGCGGCGGCGGCG-A
• chr17-62479268-AGCGGCGGCGGCG-AGCG
• chr17-62479268-AGCGGCGGCGGCG-AGCGGCG
• chr17-62479268-AGCGGCGGCGGCG-AGCGGCGGCG
• chr17-62479268-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCG
• chr17-62479268-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCG
• chr17-62479268-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006852.6(TLK2):​c.-26_-16delCGGCGGCGGCG variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TLK2 NM_006852.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.-26_-16delCGGCGGCGGCG		5_prime_UTR	Exon 1 of 22	NP_006843.2
	TLK2	NM_001284333.3		c.-23_-13delCGGCGGCGGCG		5_prime_UTR	Exon 1 of 23	NP_001271262.1	Q86UE8-1
	TLK2	NM_001375270.1		c.-23_-13delCGGCGGCGGCG		5_prime_UTR	Exon 1 of 22	NP_001362199.1	Q86UE8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLK2	ENST00000346027.10	TSL:1 MANE Select	c.-26_-16delCGGCGGCGGCG		5_prime_UTR	Exon 1 of 22	ENSP00000275780.7	Q86UE8-2
	TLK2	ENST00000326270.13	TSL:1	c.-23_-13delCGGCGGCGGCG		5_prime_UTR	Exon 1 of 23	ENSP00000316512.9	Q86UE8-1
	TLK2	ENST00000343388.11	TSL:1	c.-26_-16delCGGCGGCGGCG		5_prime_UTR	Exon 1 of 21	ENSP00000340800.7	Q86UE8-3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-60556628;