rs2066275

Positions:

• chr10-91804558-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.199+5669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,048 control chromosomes in the GnomAD database, including 8,643 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 0.33 (8643 hom., cov: 32)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998

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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.199+5669A>G		intron_variant		ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.262+5606A>G		intron_variant			XP_011538515.1
TNKS2	XM_017016701.2	c.262+5606A>G		intron_variant			XP_016872190.1
TNKS2	XM_047425795.1	c.199+5669A>G		intron_variant			XP_047281751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.199+5669A>G		intron_variant		1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.238+5669A>G		intron_variant				ENSP00000518237.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49740 AN: 151930 Hom.: 8639 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.327 AC: 49759 AN: 152048 Hom.: 8643 Cov.: 32 AF XY: 0.340 AC XY: 25243 AN XY: 74304

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.283

Alfa AF: 0.310 Hom.: 9952

Bravo AF: 0.311

Asia WGS AF: 0.492 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.94

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: rs2066275; hg19: chr10-93564315;