10-91813227-C-T

Variant names:

• chr10-91813227-C-T
• rs11186694
• NM_025235.4:c.424+20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025235.4(TNKS2):​c.424+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,592,608 control chromosomes in the GnomAD database, including 25,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2615 hom., cov: 32)
  • Exomes 𝑓: 0.18 (22910 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-91813227-C-T is Benign according to our data. Variant chr10-91813227-C-T is described in ClinVar as Benign. ClinVar VariationId is 1333083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 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.424+20C>T		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.424+20C>T		intron	N/A	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.463+20C>T		intron	N/A	ENSP00000518237.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27663 AN: 151932 Hom.: 2615 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.194

GnomAD2 exomes AF: 0.175 AC: 43406 AN: 248272 AF XY: 0.178

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.0921

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.238

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.176 AC: 253984 AN: 1440558 Hom.: 22910 Cov.: 27 AF XY: 0.177 AC XY: 127003 AN XY: 716926

African (AFR) AF: 0.197 AC: 6501 AN: 33018

American (AMR) AF: 0.0984 AC: 4370 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 5483 AN: 25924

East Asian (EAS) AF: 0.213 AC: 8411 AN: 39514

South Asian (SAS) AF: 0.180 AC: 15401 AN: 85546

European-Finnish (FIN) AF: 0.162 AC: 8631 AN: 53308

Middle Eastern (MID) AF: 0.228 AC: 1291 AN: 5670

European-Non Finnish (NFE) AF: 0.176 AC: 192980 AN: 1093542

Other (OTH) AF: 0.183 AC: 10916 AN: 59610

GnomAD4 genome AF: 0.182 AC: 27686 AN: 152050 Hom.: 2615 Cov.: 32 AF XY: 0.180 AC XY: 13405 AN XY: 74324

African (AFR) AF: 0.190 AC: 7886 AN: 41462

American (AMR) AF: 0.151 AC: 2302 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3466

East Asian (EAS) AF: 0.218 AC: 1127 AN: 5170

South Asian (SAS) AF: 0.175 AC: 843 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1713 AN: 10562

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12350 AN: 67980

Other (OTH) AF: 0.192 AC: 406 AN: 2110

Alfa AF: 0.190 Hom.: 524

Bravo AF: 0.182

Asia WGS AF: 0.197 AC: 690 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.25
PhyloP100		-1.3
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: rs11186694; hg19: chr10-93572984; COSMIC: COSV65415054;