dbSNP rs11186694: TNKS2:c.424+20C>T (chr10-91813227-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025235.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	NM_025235.4	MANE Select	c.424+20C>T		intron	N/A	NP_079511.1	Q9H2K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	ENST00000371627.5	TSL:1 MANE Select	c.424+20C>T		intron	N/A	ENSP00000360689.4	Q9H2K2
	TNKS2	ENST00000710380.1		c.463+20C>T		intron	N/A	ENSP00000518237.1	A0AA34QVI1

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

GnomAD2 exomes

AF:

0.175

AC:

43406

AN:

248272

AF XY:

0.178

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 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

African (AFR)

AF:

0.197

AC:

6501

AN:

33018

American (AMR)

AF:

0.0984

AC:

4370

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

5483

AN:

25924

East Asian (EAS)

AF:

0.213

AC:

8411

AN:

39514

South Asian (SAS)

AF:

0.180

AC:

15401

AN:

85546

European-Finnish (FIN)

AF:

0.162

AC:

8631

AN:

53308

Middle Eastern (MID)

AF:

0.228

AC:

1291

AN:

5670

European-Non Finnish (NFE)

AF:

0.176

AC:

192980

AN:

1093542

Other (OTH)

AF:

0.183

AC:

10916

AN:

59610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

10752

21504

32257

43009

53761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6818

13636

20454

27272

34090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.182

AC:

27686

AN:

152050

Hom.:

2615

Cov.:

AF XY:

0.180

AC XY:

13405

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.190

AC:

7886

AN:

41462

American (AMR)

AF:

0.151

AC:

2302

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

778

AN:

3466

East Asian (EAS)

AF:

0.218

AC:

1127

AN:

5170

South Asian (SAS)

AF:

0.175

AC:

843

AN:

4816

European-Finnish (FIN)

AF:

0.162

AC:

1713

AN:

10562

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12350

AN:

67980

Other (OTH)

AF:

0.192

AC:

406

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1150

2300

3451

4601

5751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.190

Hom.:

524

Bravo

AF:

0.182

Asia WGS

AF:

0.197

AC:

690

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.21

(source)

DANN

Benign

0.25

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over