rs17107140

chr10-91840723-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.201

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 -14 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 id is 1335822.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
TNKS2	NM_025235.4	c.1673+17G>A		intron_variant		ENST00000371627.5
TNKS2	XM_011540213.2	c.1736+17G>A		intron_variant
TNKS2	XM_017016699.2	c.1352+17G>A		intron_variant
TNKS2	XM_017016700.3	c.377+17G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.1673+17G>A		intron_variant		1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.1712+17G>A		intron_variant

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

GnomAD3 exomes AF: 0.120 AC: 29410 AN: 244542 Hom.: 2218 AF XY: 0.119 AC XY: 15684 AN XY: 132188

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 SAS exome AF: 0.160

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

Gnomad4 AFR exome AF: 0.0726

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.0891

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.0900

Gnomad4 NFE exome AF: 0.0838

Gnomad4 OTH exome AF: 0.0934

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

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0894 Hom.: 725

Bravo AF: 0.0984

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.2
Dann	Benign	0.43

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: rs17107140; hg19: chr10-93600480; COSMIC: COSV65414798;