10-91834033-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025235.4(TNKS2):c.1447+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,541,520 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (57 hom.)
• Consequence: TNKS2 NM_025235.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.243

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-91834033-T-G is Benign according to our data. Variant chr10-91834033-T-G is described in ClinVar as [Benign]. Clinvar id is 780884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNKS2	NM_025235.4	c.1447+9T>G		intron_variant		ENST00000371627.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNKS2	ENST00000371627.5	c.1447+9T>G		intron_variant		1	NM_025235.4	P1
TNKS2	ENST00000710380.1	c.1486+9T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2158 AN: 152194 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00426 AC: 911 AN: 213964 Hom.: 26 AF XY: 0.00303 AC XY: 354 AN XY: 116644

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.00291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000423

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000681

Gnomad OTH exome AF: 0.00240

GnomAD4 exome AF: 0.00150 AC: 2082 AN: 1389208 Hom.: 57 Cov.: 30 AF XY: 0.00133 AC XY: 914 AN XY: 686484

Gnomad4 AFR exome AF: 0.0563

Gnomad4 AMR exome AF: 0.00323

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000316

Gnomad4 OTH exome AF: 0.00337

GnomAD4 genome AF: 0.0142 AC: 2162 AN: 152312 Hom.: 39 Cov.: 32 AF XY: 0.0139 AC XY: 1035 AN XY: 74472

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00413 Hom.: 4

Bravo AF: 0.0168

Asia WGS AF: 0.00347 AC: 12 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.7
Dann	Benign	0.45

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: rs115905849; hg19: chr10-93593790;