17-62479268-AGCG-A

Position:

• chr17-62479268-AGCG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006852.6(TLK2):​c.-10_-8del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000531 in 150,604 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0085 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLK2 NM_006852.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04

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 -10 ACMG points.

• BP6: Variant 17-62479268-AGCG-A is Benign according to our data. Variant chr17-62479268-AGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1301690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000531 (8/150604) while in subpopulation SAS AF= 0.000208 (1/4798). AF 95% confidence interval is 0.0000477. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLK2	NM_006852.6	c.-10_-8del		5_prime_UTR_variant	1/22	ENST00000346027.10	NP_006843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLK2	ENST00000346027.10	c.-10_-8del		5_prime_UTR_variant	1/22	1	NM_006852.6	ENSP00000275780	P3

Frequencies

GnomAD3 genomes AF: 0.0000532 AC: 8 AN: 150504 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00845 AC: 129 AN: 15266 Hom.: 0 AF XY: 0.00958 AC XY: 109 AN XY: 11380

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.00943

Gnomad4 EAS exome AF: 0.00772

Gnomad4 SAS exome AF: 0.00315

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.00872

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0000531 AC: 8 AN: 150604 Hom.: 0 Cov.: 31 AF XY: 0.0000680 AC XY: 5 AN XY: 73560

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Jan 02, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs768508482; hg19: chr17-60556629;