rs17107140

Variant names:

• chr10-91840723-G-A
• rs17107140
• NM_025235.4:c.1673+17G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025235.4(TNKS2):​c.1673+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 1,601,052 control chromosomes in the GnomAD database, including 8,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (763 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7806 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.201
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-91840723-G-A is Benign according to our data. Variant chr10-91840723-G-A is described in ClinVar as Benign. ClinVar VariationId is 1335822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.1673+17G>A		intron_variant	Intron 14 of 26	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.1736+17G>A		intron_variant	Intron 14 of 26		XP_011538515.1
TNKS2	XM_017016699.2	c.1352+17G>A		intron_variant	Intron 13 of 25		XP_016872188.1
TNKS2	XM_017016700.3	c.377+17G>A		intron_variant	Intron 2 of 14		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.1673+17G>A		intron_variant	Intron 14 of 26	1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.1712+17G>A		intron_variant	Intron 14 of 26			ENSP00000518237.1
ENSG00000302365	ENST00000786181.1	n.202-3733C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14320 AN: 152042 Hom.: 759 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0993

GnomAD2 exomes AF: 0.120 AC: 29410 AN: 244542 AF XY: 0.119

Gnomad AFR exome AF: 0.0778

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.0925

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.0893

Gnomad NFE exome AF: 0.0869

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0961 AC: 139247 AN: 1448892 Hom.: 7806 Cov.: 30 AF XY: 0.0978 AC XY: 70378 AN XY: 719926

African (AFR) AF: 0.0726 AC: 2411 AN: 33208

American (AMR) AF: 0.200 AC: 8590 AN: 42932

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 2291 AN: 25718

East Asian (EAS) AF: 0.229 AC: 9004 AN: 39400

South Asian (SAS) AF: 0.160 AC: 13462 AN: 84138

European-Finnish (FIN) AF: 0.0900 AC: 4780 AN: 53130

Middle Eastern (MID) AF: 0.0973 AC: 557 AN: 5722

European-Non Finnish (NFE) AF: 0.0838 AC: 92563 AN: 1104810

Other (OTH) AF: 0.0934 AC: 5589 AN: 59834

GnomAD4 genome AF: 0.0942 AC: 14328 AN: 152160 Hom.: 763 Cov.: 32 AF XY: 0.0970 AC XY: 7220 AN XY: 74400

African (AFR) AF: 0.0776 AC: 3224 AN: 41524

American (AMR) AF: 0.137 AC: 2088 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1005 AN: 5172

South Asian (SAS) AF: 0.147 AC: 705 AN: 4812

European-Finnish (FIN) AF: 0.0902 AC: 956 AN: 10594

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0852 AC: 5795 AN: 67980

Other (OTH) AF: 0.101 AC: 214 AN: 2116

Alfa AF: 0.0902 Hom.: 964

Bravo AF: 0.0984

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 21, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.43
PhyloP100		0.20
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: rs17107140; hg19: chr10-93600480; COSMIC: COSV65414798;