10-91847668-T-C

Position:

• chr10-91847668-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.2359-715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,178 control chromosomes in the GnomAD database, including 1,571 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 (1571 hom., cov: 33)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

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=-0.86).
• 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	Protein	UniProt
TNKS2	NM_025235.4	c.2359-715T>C		intron_variant		ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.2422-715T>C		intron_variant			XP_011538515.1
TNKS2	XM_017016699.2	c.2038-715T>C		intron_variant			XP_016872188.1
TNKS2	XM_017016700.3	c.1063-715T>C		intron_variant			XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.2359-715T>C		intron_variant		1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.2398-715T>C		intron_variant				ENSP00000518237.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21169 AN: 152060 Hom.: 1569 Cov.: 33

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: 0.118

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.139 AC: 21195 AN: 152178 Hom.: 1571 Cov.: 33 AF XY: 0.136 AC XY: 10146 AN XY: 74404

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.149

Alfa AF: 0.108 Hom.: 247

Bravo AF: 0.137

Asia WGS AF: 0.0850 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	16
DANN	Benign	0.71

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: rs1772186; hg19: chr10-93607425;