rs2258946

Positions:

• chr10-91864915-G-A

Variant summary

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

The NM_025235.4(TNKS2):​c.*1916G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,518 control chromosomes in the GnomAD database, including 1,582 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 0.14 (1576 hom., cov: 32)
  • Exomes 𝑓: 0.16 (6 hom.)
• Consequence: TNKS2 NM_025235.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.*1916G>A		3_prime_UTR_variant	27/27	ENST00000371627.5
TNKS2	XM_011540213.2	c.*1916G>A		3_prime_UTR_variant	27/27
TNKS2	XM_017016699.2	c.*1916G>A		3_prime_UTR_variant	26/26
TNKS2	XM_017016700.3	c.*1916G>A		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.*1916G>A		3_prime_UTR_variant	27/27	1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.*1916G>A		3_prime_UTR_variant	27/27

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21181 AN: 151968 Hom.: 1574 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.155 AC: 67 AN: 432 Hom.: 6 Cov.: 0 AF XY: 0.169 AC XY: 44 AN XY: 260

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.139 AC: 21207 AN: 152086 Hom.: 1576 Cov.: 32 AF XY: 0.137 AC XY: 10160 AN XY: 74366

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0119

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.149

Alfa AF: 0.150 Hom.: 2335

Bravo AF: 0.137

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2258946; hg19: chr10-93624672;