chr10-91864915-G-A

Variant names:

• chr10-91864915-G-A
• rs2258946
• NM_025235.4:c.*1916G>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.*1916G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,518 control chromosomes in the GnomAD database, including 1,582 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 0.14 (1576 hom., cov: 32)
  • Exomes 𝑓: 0.16 (6 hom.)
• Consequence: TNKS2 NM_025235.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 15 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 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.*1916G>A		3_prime_UTR	Exon 27 of 27	NP_079511.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNKS2	ENST00000371627.5	TSL:1 MANE Select	c.*1916G>A		3_prime_UTR	Exon 27 of 27	ENSP00000360689.4
	TNKS2	ENST00000710380.1		c.*1916G>A		3_prime_UTR	Exon 27 of 27	ENSP00000518237.1
	ENSG00000302365	ENST00000786181.1		n.201+18113C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21181 AN: 151968 Hom.: 1574 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.155 AC: 67 AN: 432 Hom.: 6 Cov.: 0 AF XY: 0.169 AC XY: 44 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.153 AC: 65 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.139 AC: 21207 AN: 152086 Hom.: 1576 Cov.: 32 AF XY: 0.137 AC XY: 10160 AN XY: 74366

African (AFR) AF: 0.133 AC: 5518 AN: 41480

American (AMR) AF: 0.122 AC: 1860 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3468

East Asian (EAS) AF: 0.0119 AC: 62 AN: 5190

South Asian (SAS) AF: 0.121 AC: 585 AN: 4820

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10578

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10385 AN: 67966

Other (OTH) AF: 0.149 AC: 314 AN: 2106

Alfa AF: 0.150 Hom.: 2939

Bravo AF: 0.137

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2258946; hg19: chr10-93624672;