10-91842188-C-CA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_025235.4(TNKS2):c.1865dup(p.Asn622LysfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00073 in 1,373,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNKS2 NM_025235.4 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.471

Genes affected

TNKS2 (HGNC:15677): (tankyrase 2) Enables NAD+ ADP-ribosyltransferase activity; enzyme binding activity; and protein ADP-ribosylase activity. Involved in several processes, including protein ADP-ribosylation; protein localization to chromosome, telomeric region; and regulation of telomere maintenance. Located in nuclear envelope; pericentriolar material; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.1865dup	p.Asn622LysfsTer12	frameshift_variant	16/27	ENST00000371627.5
TNKS2	XM_011540213.2	c.1928dup	p.Asn643LysfsTer12	frameshift_variant	16/27
TNKS2	XM_017016699.2	c.1544dup	p.Asn515LysfsTer12	frameshift_variant	15/26
TNKS2	XM_017016700.3	c.569dup	p.Asn190LysfsTer12	frameshift_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.1865dup	p.Asn622LysfsTer12	frameshift_variant	16/27	1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.1904dup	p.Asn635LysfsTer12	frameshift_variant	16/27

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149190 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000730 AC: 1003 AN: 1373192 Hom.: 0 Cov.: 31 AF XY: 0.000686 AC XY: 469 AN XY: 683926

Gnomad4 AFR exome AF: 0.000736

Gnomad4 AMR exome AF: 0.000474

Gnomad4 ASJ exome AF: 0.000618

Gnomad4 EAS exome AF: 0.000324

Gnomad4 SAS exome AF: 0.000505

Gnomad4 FIN exome AF: 0.000296

Gnomad4 NFE exome AF: 0.000798

Gnomad4 OTH exome AF: 0.000708

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72590

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00806 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

CIC-DUX Sarcoma Other:1

not provided, no classification provided

literature only

Children's Cancer Therapy Development Institute

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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: rs749004712; hg19: chr10-93601945;