rs3756819

Variant names:

• chr6-24665112-A-C
• rs3756819
• NM_016614.3:c.251+1414T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016614.3(TDP2):​c.251+1414T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,180 control chromosomes in the GnomAD database, including 2,027 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 0.16 (2027 hom., cov: 32)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDP2	NM_016614.3	c.251+1414T>G		intron_variant	Intron 2 of 6	ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.251+1414T>G		intron_variant	Intron 2 of 6	1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.77+1007T>G		intron_variant	Intron 1 of 5	1		ENSP00000345345.3
TDP2	ENST00000478507.1	n.319+1414T>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24045 AN: 152062 Hom.: 2027 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24039 AN: 152180 Hom.: 2027 Cov.: 32 AF XY: 0.156 AC XY: 11633 AN XY: 74400

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.161

Alfa AF: 0.154 Hom.: 2386

Bravo AF: 0.159

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.52

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: rs3756819; hg19: chr6-24665340;