rs10881982

chr10-91855239-T-Achr10-91855239-T-C

Variant summary

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

The NM_025235.4(TNKS2):c.2913+113T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 713,188 control chromosomes in the GnomAD database, including 1,205 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 0.039 (223 hom., cov: 32)
  • Exomes 𝑓: 0.040 (982 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.2913+113T>A		intron_variant		ENST00000371627.5
TNKS2	XM_011540213.2	c.2976+113T>A		intron_variant
TNKS2	XM_017016699.2	c.2592+113T>A		intron_variant
TNKS2	XM_017016700.3	c.1617+113T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.2913+113T>A		intron_variant		1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.2952+113T>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5926 AN: 152128 Hom.: 224 Cov.: 32

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0430

GnomAD4 exome AF: 0.0404 AC: 22650 AN: 560942 Hom.: 982 AF XY: 0.0410 AC XY: 12390 AN XY: 302226

Gnomad4 AFR exome AF: 0.0417

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0288

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.0485

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0295

Gnomad4 OTH exome AF: 0.0413

GnomAD4 genome AF: 0.0389 AC: 5923 AN: 152246 Hom.: 223 Cov.: 32 AF XY: 0.0399 AC XY: 2969 AN XY: 74458

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0114

Gnomad4 NFE AF: 0.0287

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0310 Hom.: 12

Bravo AF: 0.0412

Asia WGS AF: 0.111 AC: 387 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.043
Dann	Benign	0.18

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: rs10881982; hg19: chr10-93614996;