10-91844121-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.2060-798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,244 control chromosomes in the GnomAD database, including 989 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 0.11 (989 hom., cov: 33)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.2060-798A>G		intron_variant		ENST00000371627.5
TNKS2	XM_011540213.2	c.2123-798A>G		intron_variant
TNKS2	XM_017016699.2	c.1739-798A>G		intron_variant
TNKS2	XM_017016700.3	c.764-798A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.2060-798A>G		intron_variant		1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.2099-798A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16473 AN: 152126 Hom.: 983 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.108 AC: 16496 AN: 152244 Hom.: 989 Cov.: 33 AF XY: 0.111 AC XY: 8229 AN XY: 74438

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.0937

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0934 Hom.: 85

Bravo AF: 0.113

Asia WGS AF: 0.158 AC: 547 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.8
Dann	Benign	0.85
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: rs10509639; hg19: chr10-93603878;