10-91817384-T-G

Position:

• chr10-91817384-T-G

Variant summary

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

The NM_025235.4(TNKS2):​c.520+155T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,220 control chromosomes in the GnomAD database, including 46,085 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 0.77 (46085 hom., cov: 33)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.520+155T>G		intron_variant		ENST00000371627.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.520+155T>G		intron_variant		1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.559+155T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117601 AN: 152102 Hom.: 46041 Cov.: 33

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.773 AC: 117703 AN: 152220 Hom.: 46085 Cov.: 33 AF XY: 0.782 AC XY: 58160 AN XY: 74418

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.724

Alfa AF: 0.727 Hom.: 18454

Bravo AF: 0.769

Asia WGS AF: 0.891 AC: 3101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.69

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: rs1539041; hg19: chr10-93577141;