chr10-91848385-G-A

Variant names:

• chr10-91848385-G-A
• rs3758499
• NM_025235.4:c.2361G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_025235.4(TNKS2):​c.2361G>A​(p.Ala787Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,613,252 control chromosomes in the GnomAD database, including 93,314 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 0.33 (8618 hom., cov: 32)
  • Exomes 𝑓: 0.33 (84696 hom.)
• Consequence: TNKS2 NM_025235.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 25 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNKS2	NM_025235.4	c.2361G>A	p.Ala787Ala	splice_region_variant, synonymous_variant	Exon 19 of 27	ENST00000371627.5	NP_079511.1
TNKS2	XM_011540213.2	c.2424G>A	p.Ala808Ala	splice_region_variant, synonymous_variant	Exon 19 of 27		XP_011538515.1
TNKS2	XM_017016699.2	c.2040G>A	p.Ala680Ala	splice_region_variant, synonymous_variant	Exon 18 of 26		XP_016872188.1
TNKS2	XM_017016700.3	c.1065G>A	p.Ala355Ala	splice_region_variant, synonymous_variant	Exon 7 of 15		XP_016872189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNKS2	ENST00000371627.5	c.2361G>A	p.Ala787Ala	splice_region_variant, synonymous_variant	Exon 19 of 27	1	NM_025235.4	ENSP00000360689.4
TNKS2	ENST00000710380.1	c.2400G>A	p.Ala800Ala	splice_region_variant, synonymous_variant	Exon 19 of 27			ENSP00000518237.1
ENSG00000302365	ENST00000786181.1	n.202-11395C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49576 AN: 151858 Hom.: 8613 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.381 AC: 95354 AN: 250466 AF XY: 0.382

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.471

Gnomad FIN exome AF: 0.449

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.333 AC: 486025 AN: 1461276 Hom.: 84696 Cov.: 36 AF XY: 0.337 AC XY: 244630 AN XY: 726878

African (AFR) AF: 0.241 AC: 8058 AN: 33476

American (AMR) AF: 0.466 AC: 20840 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 10438 AN: 26116

East Asian (EAS) AF: 0.490 AC: 19434 AN: 39690

South Asian (SAS) AF: 0.492 AC: 42409 AN: 86224

European-Finnish (FIN) AF: 0.440 AC: 23494 AN: 53402

Middle Eastern (MID) AF: 0.273 AC: 1576 AN: 5764

European-Non Finnish (NFE) AF: 0.305 AC: 339483 AN: 1111574

Other (OTH) AF: 0.336 AC: 20293 AN: 60340

GnomAD4 genome AF: 0.326 AC: 49595 AN: 151976 Hom.: 8618 Cov.: 32 AF XY: 0.339 AC XY: 25179 AN XY: 74274

African (AFR) AF: 0.251 AC: 10385 AN: 41444

American (AMR) AF: 0.382 AC: 5839 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1340 AN: 3464

East Asian (EAS) AF: 0.499 AC: 2580 AN: 5166

South Asian (SAS) AF: 0.529 AC: 2552 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4899 AN: 10544

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 21018 AN: 67956

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.302 Hom.: 11109

Bravo AF: 0.310

Asia WGS AF: 0.493 AC: 1713 AN: 3478

EpiCase AF: 0.295

EpiControl AF: 0.294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.39
PhyloP100		-0.069
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.29		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3758499; hg19: chr10-93608142; COSMIC: COSV65415049;