Genetic Variant TNKS2:c.*1261C>G (chr10-91864260-C-G) – 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.*1261C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,368 control chromosomes in the GnomAD database, including 20,854 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 0.52 ( 20767 hom., cov: 31)

Exomes 𝑓: 0.62 ( 87 hom. )

Consequence

TNKS2
NM_025235.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.470

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:

ENSG00000302365 (HGNC:):

ENSG00000302365 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TNKS2	NM_025235.4 link	c.*1261C>G	3_prime_UTR_variant	Exon 27 of 27	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2 link	c.*1261C>G	3_prime_UTR_variant	Exon 27 of 27		XP_011538515.1
TNKS2	XM_017016699.2 link	c.*1261C>G	3_prime_UTR_variant	Exon 26 of 26		XP_016872188.1
TNKS2	XM_017016700.3 link	c.*1261C>G	3_prime_UTR_variant	Exon 15 of 15		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5 link	c.*1261C>G		3_prime_UTR_variant	Exon 27 of 27	1	NM_025235.4	ENSP00000360689.4

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

78518

AN:

151816

Hom.:

20745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.561

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.706

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.488

GnomAD4 exome

AF:

0.620

AC:

269

AN:

434

Hom.:

Cov.:

AF XY:

0.630

AC XY:

165

AN XY:

262

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.620

AC:

264

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.517

AC:

78581

AN:

151934

Hom.:

20767

Cov.:

AF XY:

0.528

AC XY:

39206

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.469

AC:

19457

AN:

41442

American (AMR)

AF:

0.538

AC:

8211

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

2134

AN:

3458

East Asian (EAS)

AF:

0.717

AC:

3702

AN:

5162

South Asian (SAS)

AF:

0.704

AC:

3400

AN:

4828

European-Finnish (FIN)

AF:

0.626

AC:

6613

AN:

10556

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.491

AC:

33372

AN:

67924

Other (OTH)

AF:

0.485

AC:

1021

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1868

3736

5603

7471

9339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.502

Hom.:

2482

Bravo

AF:

0.502

Asia WGS

AF:

0.699

AC:

2433

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.86

(source)

DANN

Benign

0.50

PhyloP100

0.47

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over