rs139153310

Variant names:

• chr6-24657828-A-C
• rs139153310
• NM_016614.3:c.501T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-24657828-A-C
• chr6-24657828-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016614.3(TDP2):​c.501T>G​(p.Asn167Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TDP2 NM_016614.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

Genes affected

TDP2 (HGNC:17768): (tyrosyl-DNA phosphodiesterase 2) This gene encodes a member of a superfamily of divalent cation-dependent phosphodiesterases. The encoded protein associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. This protein has sequence and structural similarities with APE1 endonuclease, which is involved in both DNA repair and the activation of transcription factors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDP2	NM_016614.3	c.501T>G	p.Asn167Lys	missense_variant	Exon 4 of 7	ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.501T>G	p.Asn167Lys	missense_variant	Exon 4 of 7	1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.327T>G	p.Asn109Lys	missense_variant	Exon 3 of 6	1		ENSP00000345345.3
TDP2	ENST00000478285.1	n.688T>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
TDP2	ENST00000478507.1	n.320-4675T>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	26
DANN	Benign	0.94
DEOGEN2	Benign	0.089	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.22
Sift	Benign	0.082	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.0010	B;.
Vest4		0.38
MutPred		0.56		Gain of ubiquitination at N167 (P = 0.0325);.;
MVP		0.65
MPC		0.19
ClinPred		0.53	D
GERP RS		4.9
Varity_R		0.078
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.99		Position offset: 5
DS_DL_spliceai		0.91		Position offset: -16

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

Publications

LitVar

Other links and lift over

dbSNP: rs139153310; hg19: chr6-24658056;