rs2066275

Variant names:

• chr10-91804558-A-G
• rs2066275
• NM_025235.4:c.199+5669A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.199+5669A>G		intron_variant	Intron 1 of 26	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.262+5606A>G		intron_variant	Intron 1 of 26		XP_011538515.1
TNKS2	XM_017016701.2	c.262+5606A>G		intron_variant	Intron 1 of 12		XP_016872190.1
TNKS2	XM_047425795.1	c.199+5669A>G		intron_variant	Intron 1 of 12		XP_047281751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.199+5669A>G		intron_variant	Intron 1 of 26	1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.238+5669A>G		intron_variant	Intron 1 of 26			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

African (AFR) AF: 0.255 AC: 10574 AN: 41474

American (AMR) AF: 0.382 AC: 5841 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2569 AN: 5168

South Asian (SAS) AF: 0.527 AC: 2539 AN: 4816

European-Finnish (FIN) AF: 0.463 AC: 4892 AN: 10562

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21020 AN: 67960

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.310 Hom.: 12585

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
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2066275; hg19: chr10-93564315;