Variant 10-91813227-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025235.4(TNKS2):c.424+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,592,608 control chromosomes in the GnomAD database, including 25,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2615 hom., cov: 32)

Exomes 𝑓: 0.18 ( 22910 hom. )

Consequence

TNKS2
NM_025235.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.25

Variant links:

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]

TNKS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-91813227-C-T is Benign according to our data. Variant chr10-91813227-C-T is described in ClinVar as [Benign]. Clinvar id is 1333083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNKS2	NM_025235.4 linkuse as main transcript	c.424+20C>T		intron_variant		ENST00000371627.5	NP_079511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5 linkuse as main transcript	c.424+20C>T		intron_variant		1	NM_025235.4	ENSP00000360689	P1
TNKS2	ENST00000710380.1 linkuse as main transcript	c.463+20C>T		intron_variant				ENSP00000518237

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27663

AN:

151932

Hom.:

2615

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.194

GnomAD3 exomes

AF:

0.175

AC:

43406

AN:

248272

Hom.:

4099

AF XY:

0.178

AC XY:

23848

AN XY:

134160

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0921

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.176

AC:

253984

AN:

1440558

Hom.:

22910

Cov.:

AF XY:

0.177

AC XY:

127003

AN XY:

716926

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.0984

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.182

AC:

27686

AN:

152050

Hom.:

2615

Cov.:

AF XY:

0.180

AC XY:

13405

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.175

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.190

Hom.:

524

Bravo

AF:

0.182

Asia WGS

AF:

0.197

AC:

690

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.21

DANN

Benign

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over