NM_025235.4:c.2060-798A>G

Variant names:

• chr10-91844121-A-G
• rs10509639
• NM_025235.4:c.2060-798A>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.2060-798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,244 control chromosomes in the GnomAD database, including 989 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 0.11 (989 hom., cov: 33)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553
• Publications: 6 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 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.2060-798A>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.2060-798A>G		intron	N/A	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.2099-798A>G		intron	N/A	ENSP00000518237.1
	ENSG00000302365	ENST00000786181.1		n.202-7131T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16473 AN: 152126 Hom.: 983 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.108 AC: 16496 AN: 152244 Hom.: 989 Cov.: 33 AF XY: 0.111 AC XY: 8229 AN XY: 74438

African (AFR) AF: 0.108 AC: 4501 AN: 41550

American (AMR) AF: 0.144 AC: 2202 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1006 AN: 5186

South Asian (SAS) AF: 0.152 AC: 735 AN: 4826

European-Finnish (FIN) AF: 0.0932 AC: 988 AN: 10606

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0937 AC: 6376 AN: 68012

Other (OTH) AF: 0.113 AC: 238 AN: 2110

Alfa AF: 0.0942 Hom.: 94

Bravo AF: 0.113

Asia WGS AF: 0.158 AC: 547 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.8
DANN	Benign	0.85
PhyloP100		0.55
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: rs10509639; hg19: chr10-93603878;