10-91847668-T-C

Variant names:

• chr10-91847668-T-C
• rs1772186
• NM_025235.4:c.2359-715T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

ENSG00000302365 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.2359-715T>C		intron_variant	Intron 18 of 26	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.2422-715T>C		intron_variant	Intron 18 of 26		XP_011538515.1
TNKS2	XM_017016699.2	c.2038-715T>C		intron_variant	Intron 17 of 25		XP_016872188.1
TNKS2	XM_017016700.3	c.1063-715T>C		intron_variant	Intron 6 of 14		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.2359-715T>C		intron_variant	Intron 18 of 26	1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.2398-715T>C		intron_variant	Intron 18 of 26			ENSP00000518237.1
ENSG00000302365	ENST00000786181.1	n.202-10678A>G		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.133 AC: 5519 AN: 41512

American (AMR) AF: 0.122 AC: 1863 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 637 AN: 3472

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5184

South Asian (SAS) AF: 0.119 AC: 573 AN: 4822

European-Finnish (FIN) AF: 0.149 AC: 1581 AN: 10578

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10389 AN: 67994

Other (OTH) AF: 0.149 AC: 314 AN: 2112

Alfa AF: 0.126 Hom.: 500

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
PhyloP100		0.40
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: rs1772186; hg19: chr10-93607425;