10-91857549-A-G

Variant names:

• chr10-91857549-A-G
• rs1340420
• NM_025235.4:c.3094+19A>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.3094+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,541,984 control chromosomes in the GnomAD database, including 317,723 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 (38332 hom., cov: 32)
  • Exomes 𝑓: 0.63 (279391 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.57
• Publications: 13 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]

ENSG00000302365 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025235.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	NM_025235.4	MANE Select	c.3094+19A>G		intron	N/A	NP_079511.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	ENST00000371627.5	TSL:1 MANE Select	c.3094+19A>G		intron	N/A	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.3133+19A>G		intron	N/A	ENSP00000518237.1
	ENSG00000302365	ENST00000786181.1		n.202-20559T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106182 AN: 151988 Hom.: 38286 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.656

GnomAD2 exomes AF: 0.707 AC: 174075 AN: 246278 AF XY: 0.703

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.804

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.910

Gnomad FIN exome AF: 0.706

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.625 AC: 869052 AN: 1389878 Hom.: 279391 Cov.: 20 AF XY: 0.630 AC XY: 438154 AN XY: 695126

African (AFR) AF: 0.844 AC: 27048 AN: 32062

American (AMR) AF: 0.788 AC: 34454 AN: 43750

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 18621 AN: 25370

East Asian (EAS) AF: 0.931 AC: 36571 AN: 39270

South Asian (SAS) AF: 0.837 AC: 69789 AN: 83410

European-Finnish (FIN) AF: 0.694 AC: 36670 AN: 52808

Middle Eastern (MID) AF: 0.629 AC: 3528 AN: 5610

European-Non Finnish (NFE) AF: 0.576 AC: 605184 AN: 1049964

Other (OTH) AF: 0.645 AC: 37187 AN: 57634

GnomAD4 genome AF: 0.699 AC: 106283 AN: 152106 Hom.: 38332 Cov.: 32 AF XY: 0.709 AC XY: 52732 AN XY: 74354

African (AFR) AF: 0.833 AC: 34579 AN: 41514

American (AMR) AF: 0.706 AC: 10781 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2548 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4725 AN: 5184

South Asian (SAS) AF: 0.857 AC: 4138 AN: 4826

European-Finnish (FIN) AF: 0.719 AC: 7608 AN: 10582

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39817 AN: 67946

Other (OTH) AF: 0.654 AC: 1379 AN: 2110

Alfa AF: 0.656 Hom.: 6857

Bravo AF: 0.700

Asia WGS AF: 0.870 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.013
DANN	Benign	0.32
PhyloP100		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1340420; hg19: chr10-93617306;