10-91857549-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025235.4(TNKS2):c.3094+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,541,984 control chromosomes in the GnomAD database, including 317,723 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (38332 hom., cov: 32)
  • Exomes 𝑓: 0.63 (279391 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.57

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.3094+19A>G		intron_variant		ENST00000371627.5
TNKS2	XM_011540213.2	c.3157+19A>G		intron_variant
TNKS2	XM_017016699.2	c.2773+19A>G		intron_variant
TNKS2	XM_017016700.3	c.1798+19A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.3094+19A>G		intron_variant		1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.3133+19A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106182 AN: 151988 Hom.: 38286 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.656

GnomAD3 exomes AF: 0.707 AC: 174075 AN: 246278 Hom.: 63504 AF XY: 0.703 AC XY: 93839 AN XY: 133494

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.804

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.910

Gnomad SAS exome AF: 0.843

Gnomad FIN exome AF: 0.706

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.625 AC: 869052 AN: 1389878 Hom.: 279391 Cov.: 20 AF XY: 0.630 AC XY: 438154 AN XY: 695126

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.788

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.931

Gnomad4 SAS exome AF: 0.837

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.699 AC: 106283 AN: 152106 Hom.: 38332 Cov.: 32 AF XY: 0.709 AC XY: 52732 AN XY: 74354

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.654

Alfa AF: 0.656 Hom.: 6857

Bravo AF: 0.700

Asia WGS AF: 0.870 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.013
Dann	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1340420; hg19: chr10-93617306;