chr6-24650533-A-G

Position:

• chr6-24650533-A-G

Variant summary

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

The ENST00000378198.9(TDP2):​c.*255T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 461,264 control chromosomes in the GnomAD database, including 7,113 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 (2647 hom., cov: 32)
  • Exomes 𝑓: 0.16 (4466 hom.)
• Consequence: TDP2 ENST00000378198.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP2	NM_016614.3	c.*255T>C		3_prime_UTR_variant	7/7	ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.*255T>C		3_prime_UTR_variant	7/7	1	NM_016614.3	ENSP00000367440	P1
TDP2	ENST00000341060.3	c.*255T>C		3_prime_UTR_variant	6/6	1		ENSP00000345345

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27451 AN: 152142 Hom.: 2649 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.162 AC: 50206 AN: 309004 Hom.: 4466 Cov.: 3 AF XY: 0.160 AC XY: 25952 AN XY: 162456

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.0677

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.180 AC: 27470 AN: 152260 Hom.: 2647 Cov.: 32 AF XY: 0.176 AC XY: 13073 AN XY: 74454

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0404

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.198

Alfa AF: 0.179 Hom.: 3659

Bravo AF: 0.186

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.097
DANN	Benign	0.43

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: rs3087943; hg19: chr6-24650761;