10-91819544-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_025235.4(TNKS2):​c.620G>T​(p.Ser207Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,592,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TNKS2
NM_025235.4 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.97
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNKS2NM_025235.4 linkuse as main transcriptc.620G>T p.Ser207Ile missense_variant 5/27 ENST00000371627.5 NP_079511.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNKS2ENST00000371627.5 linkuse as main transcriptc.620G>T p.Ser207Ile missense_variant 5/271 NM_025235.4 ENSP00000360689 P1
TNKS2ENST00000710380.1 linkuse as main transcriptc.659G>T p.Ser220Ile missense_variant 5/27 ENSP00000518237

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152094
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000201
AC:
29
AN:
1440052
Hom.:
0
Cov.:
31
AF XY:
0.0000181
AC XY:
13
AN XY:
716338
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000244
Gnomad4 OTH exome
AF:
0.0000337
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152094
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 20, 2023The c.620G>T (p.S207I) alteration is located in exon 5 (coding exon 5) of the TNKS2 gene. This alteration results from a G to T substitution at nucleotide position 620, causing the serine (S) at amino acid position 207 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Uncertain
0.076
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.0072
T
MetaRNN
Uncertain
0.67
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-4.2
D
REVEL
Uncertain
0.36
Sift
Benign
0.034
D
Sift4G
Benign
0.096
T
Polyphen
0.42
B
Vest4
0.84
MVP
0.37
MPC
1.2
ClinPred
0.96
D
GERP RS
5.8
Varity_R
0.44
gMVP
0.58

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs757511917; hg19: chr10-93579301; API