rs3212232

Positions:

• chr6-24657669-A-G
• chr6-24657669-A-T

Variant summary

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

The NM_016614.3(TDP2):​c.517+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 380,136 control chromosomes in the GnomAD database, including 8,369 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 0.18 (2889 hom., cov: 33)
  • Exomes 𝑓: 0.21 (5480 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP2	NM_016614.3	c.517+143T>C		intron_variant		ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.517+143T>C		intron_variant		1	NM_016614.3	ENSP00000367440	P1
TDP2	ENST00000341060.3	c.343+143T>C		intron_variant		1		ENSP00000345345
TDP2	ENST00000478285.1	n.704+143T>C		intron_variant, non_coding_transcript_variant		2
TDP2	ENST00000478507.1	n.320-4516T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27723 AN: 151982 Hom.: 2888 Cov.: 33

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.210 AC: 47952 AN: 228036 Hom.: 5480 AF XY: 0.207 AC XY: 24859 AN XY: 119904

Gnomad4 AFR exome AF: 0.0821

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.182 AC: 27722 AN: 152100 Hom.: 2889 Cov.: 33 AF XY: 0.180 AC XY: 13358 AN XY: 74346

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.154

Alfa AF: 0.215 Hom.: 888

Bravo AF: 0.176

Asia WGS AF: 0.118 AC: 409 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.7
DANN	Benign	0.85

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: rs3212232; hg19: chr6-24657897;