Genetic Variant NM_025235.4:c.3094+19A>C (chr10-91857549-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025235.4(TNKS2):c.3094+19A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNKS2
NM_025235.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.57

Publications

13 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TNKS2	NM_025235.4 link	c.3094+19A>C	intron_variant	Intron 24 of 26	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2 link	c.3157+19A>C	intron_variant	Intron 24 of 26		XP_011538515.1
TNKS2	XM_017016699.2 link	c.2773+19A>C	intron_variant	Intron 23 of 25		XP_016872188.1
TNKS2	XM_017016700.3 link	c.1798+19A>C	intron_variant	Intron 12 of 14		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5 link	c.3094+19A>C		intron_variant	Intron 24 of 26	1	NM_025235.4	ENSP00000360689.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1392416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696262

African (AFR)

AF:

0.00

AC:

AN:

32086

American (AMR)

AF:

0.00

AC:

AN:

43792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25388

East Asian (EAS)

AF:

0.00

AC:

AN:

39280

South Asian (SAS)

AF:

0.00

AC:

AN:

83470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1052202

Other (OTH)

AF:

0.00

AC:

AN:

57714

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.010

(source)

DANN

Benign

0.30

PhyloP100

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over