17-62479268-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_006852.6(TLK2):​c.-13_-8dupGGCGGC variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 166,458 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 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

TLK2
NM_006852.6 splice_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.343
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000113 (17/150516) while in subpopulation AFR AF= 0.000293 (12/40978). AF 95% confidence interval is 0.000168. 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 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLK2NM_006852.6 linkc.-13_-8dupGGCGGC splice_region_variant Exon 1 of 22 ENST00000346027.10 NP_006843.2 Q86UE8-2
TLK2NM_006852.6 linkc.-13_-8dupGGCGGC 5_prime_UTR_variant Exon 1 of 22 ENST00000346027.10 NP_006843.2 Q86UE8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLK2ENST00000346027.10 linkc.-13_-8dupGGCGGC splice_region_variant Exon 1 of 22 1 NM_006852.6 ENSP00000275780.7 Q86UE8-2
TLK2ENST00000346027 linkc.-13_-8dupGGCGGC 5_prime_UTR_variant Exon 1 of 22 1 NM_006852.6 ENSP00000275780.7 Q86UE8-2

Frequencies

GnomAD3 genomes
AF:
0.000113
AC:
17
AN:
150516
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000293
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.0000967
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000125
AC:
2
AN:
15942
Hom.:
0
Cov.:
0
AF XY:
0.000168
AC XY:
2
AN XY:
11904
show subpopulations
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:
0.00649
Gnomad4 NFE exome
AF:
0.0000779
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000113
AC:
17
AN:
150516
Hom.:
0
Cov.:
31
AF XY:
0.000109
AC XY:
8
AN XY:
73456
show subpopulations
Gnomad4 AFR
AF:
0.000293
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.0000967
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs768508482; hg19: chr17-60556629; API