rs1572934

Positions:

• chr10-91828451-G-A
• chr10-91828451-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.1104+45G>A		intron_variant		ENST00000371627.5	NP_079511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.1104+45G>A		intron_variant		1	NM_025235.4	ENSP00000360689	P1
TNKS2	ENST00000710380.1	c.1143+45G>A		intron_variant				ENSP00000518237

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105823 AN: 151612 Hom.: 38097 Cov.: 33

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

GnomAD3 exomes AF: 0.690 AC: 118472 AN: 171742 Hom.: 41905 AF XY: 0.683 AC XY: 64285 AN XY: 94056

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 SAS exome AF: 0.844

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.: 22 AF XY: 0.620 AC XY: 404747 AN XY: 653124

Gnomad4 AFR exome AF: 0.843

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.732

Gnomad4 EAS exome AF: 0.934

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.698 AC: 105924 AN: 151730 Hom.: 38143 Cov.: 33 AF XY: 0.708 AC XY: 52504 AN XY: 74124

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.653

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
DANN	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs1572934; hg19: chr10-93588208;