10-91817867-A-G

Variant names:

• chr10-91817867-A-G
• rs3802650
• NM_025235.4:c.520+638A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025235.4(TNKS2):​c.520+638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,014 control chromosomes in the GnomAD database, including 20,297 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 0.51 (20297 hom., cov: 32)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 9 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.520+638A>G		intron_variant	Intron 3 of 26	ENST00000371627.5	NP_079511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.520+638A>G		intron_variant	Intron 3 of 26	1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.559+638A>G		intron_variant	Intron 3 of 26			ENSP00000518237.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77575 AN: 151896 Hom.: 20276 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.511 AC: 77632 AN: 152014 Hom.: 20297 Cov.: 32 AF XY: 0.521 AC XY: 38740 AN XY: 74312

African (AFR) AF: 0.447 AC: 18505 AN: 41436

American (AMR) AF: 0.536 AC: 8200 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2123 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3708 AN: 5172

South Asian (SAS) AF: 0.704 AC: 3397 AN: 4824

European-Finnish (FIN) AF: 0.626 AC: 6607 AN: 10550

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33408 AN: 67954

Other (OTH) AF: 0.481 AC: 1016 AN: 2112

Alfa AF: 0.496 Hom.: 23675

Bravo AF: 0.494

Asia WGS AF: 0.698 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3802650; hg19: chr10-93577624;