Genetic Variant TNKS2:c.1104+45G>A (chr10-91828451-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025235.4(TNKS2):c.1104+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 1,476,122 control chromosomes in the GnomAD database, including 295,547 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 0.70 ( 38143 hom., cov: 33)

Exomes 𝑓: 0.61 ( 257404 hom. )

Consequence

TNKS2
NM_025235.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Publications

12 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS2	NM_025235.4 link	c.1104+45G>A		intron_variant	Intron 9 of 26	ENST00000371627.5	NP_079511.1	Q9H2K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5 link	c.1104+45G>A		intron_variant	Intron 9 of 26	1	NM_025235.4	ENSP00000360689.4		Q9H2K2
TNKS2	ENST00000710380.1 link	c.1143+45G>A		intron_variant	Intron 9 of 26			ENSP00000518237.1

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

105823

AN:

151612

Hom.:

38097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.734

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.858

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.655

GnomAD2 exomes

AF:

0.690

AC:

118472

AN:

171742

AF XY:

0.683

show subpopulations

Gnomad AFR exome

AF:

0.837

Gnomad AMR exome

AF:

0.804

Gnomad ASJ exome

AF:

0.743

Gnomad EAS exome

AF:

0.908

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.615

AC:

814073

AN:

1324392

Hom.:

257404

Cov.:

AF XY:

0.620

AC XY:

404747

AN XY:

653124

show subpopulations

African (AFR)

AF:

0.843

AC:

23439

AN:

27812

American (AMR)

AF:

0.783

AC:

21094

AN:

26946

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

15775

AN:

21544

East Asian (EAS)

AF:

0.934

AC:

32490

AN:

34780

South Asian (SAS)

AF:

0.836

AC:

56550

AN:

67640

European-Finnish (FIN)

AF:

0.694

AC:

34953

AN:

50364

Middle Eastern (MID)

AF:

0.624

AC:

3312

AN:

5306

European-Non Finnish (NFE)

AF:

0.571

AC:

591856

AN:

1035696

Other (OTH)

AF:

0.637

AC:

34604

AN:

54304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

12067

24134

36202

48269

60336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17162

34324

51486

68648

85810

<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:

0.698

AC:

105924

AN:

151730

Hom.:

38143

Cov.:

AF XY:

0.708

AC XY:

52504

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.833

AC:

34464

AN:

41396

American (AMR)

AF:

0.705

AC:

10765

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

2546

AN:

3468

East Asian (EAS)

AF:

0.911

AC:

4714

AN:

5174

South Asian (SAS)

AF:

0.857

AC:

4138

AN:

4826

European-Finnish (FIN)

AF:

0.718

AC:

7519

AN:

10476

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.585

AC:

39688

AN:

67816

Other (OTH)

AF:

0.653

AC:

1375

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1573

3147

4720

6294

7867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.616

Hom.:

4399

Bravo

AF:

0.700

Asia WGS

AF:

0.870

AC:

3027

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.1

(source)

DANN

Benign

0.83

PhyloP100

0.016

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over