rs1538833

Variant names:

• chr10-91844596-G-A
• rs1538833
• NM_025235.4:c.2060-323G>A

Variant summary

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

The NM_025235.4(TNKS2):​c.2060-323G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 152,182 control chromosomes in the GnomAD database, including 766 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 0.094 (766 hom., cov: 32)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 3 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=-0.87).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	NM_025235.4	MANE Select	c.2060-323G>A		intron	N/A	NP_079511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	ENST00000371627.5	TSL:1 MANE Select	c.2060-323G>A		intron	N/A	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.2099-323G>A		intron	N/A	ENSP00000518237.1
	ENSG00000302365	ENST00000786181.1		n.202-7606C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14326 AN: 152064 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0889

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.0991

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

GnomAD4 genome AF: 0.0942 AC: 14334 AN: 152182 Hom.: 766 Cov.: 32 AF XY: 0.0970 AC XY: 7219 AN XY: 74394

African (AFR) AF: 0.0776 AC: 3221 AN: 41514

American (AMR) AF: 0.136 AC: 2084 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0889 AC: 308 AN: 3464

East Asian (EAS) AF: 0.194 AC: 1004 AN: 5172

South Asian (SAS) AF: 0.147 AC: 707 AN: 4820

European-Finnish (FIN) AF: 0.0906 AC: 961 AN: 10606

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0853 AC: 5803 AN: 68008

Other (OTH) AF: 0.101 AC: 213 AN: 2110

Alfa AF: 0.0939 Hom.: 425

Bravo AF: 0.0984

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.7
DANN	Benign	0.29
PhyloP100		0.0020
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: rs1538833; hg19: chr10-93604353;