10-91833770-G-T

Position:

• chr10-91833770-G-T

Variant summary

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

The NM_025235.4(TNKS2):​c.1276-83G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,115,968 control chromosomes in the GnomAD database, including 18,620 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 0.19 (2810 hom., cov: 33)
  • Exomes 𝑓: 0.18 (15810 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.1276-83G>T		intron_variant		ENST00000371627.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.1276-83G>T		intron_variant		1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.1315-83G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28619 AN: 152034 Hom.: 2804 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.178 AC: 171737 AN: 963816 Hom.: 15810 AF XY: 0.179 AC XY: 84699 AN XY: 473880

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.188 AC: 28658 AN: 152152 Hom.: 2810 Cov.: 33 AF XY: 0.187 AC XY: 13887 AN XY: 74390

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.200

Alfa AF: 0.148 Hom.: 449

Bravo AF: 0.190

Asia WGS AF: 0.203 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.65

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: rs1770474; hg19: chr10-93593527; COSMIC: COSV65415060;