6-24657736-T-G

Position:

• chr6-24657736-T-G

Variant summary

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

The NM_016614.3(TDP2):​c.517+76A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 793,824 control chromosomes in the GnomAD database, including 79,982 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 0.39 (12711 hom., cov: 32)
  • Exomes 𝑓: 0.45 (67271 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP2	NM_016614.3	c.517+76A>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+76A>C		intron_variant		1	NM_016614.3	ENSP00000367440	P1
TDP2	ENST00000341060.3	c.343+76A>C		intron_variant		1		ENSP00000345345
TDP2	ENST00000478285.1	n.704+76A>C		intron_variant, non_coding_transcript_variant		2
TDP2	ENST00000478507.1	n.320-4583A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59604 AN: 151906 Hom.: 12714 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.446 AC: 286081 AN: 641800 Hom.: 67271 AF XY: 0.441 AC XY: 148241 AN XY: 336020

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.499

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.392 AC: 59626 AN: 152024 Hom.: 12711 Cov.: 32 AF XY: 0.388 AC XY: 28848 AN XY: 74304

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.367

Alfa AF: 0.428 Hom.: 4684

Bravo AF: 0.377

Asia WGS AF: 0.242 AC: 835 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0020
DANN	Benign	0.75

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: rs3212231; hg19: chr6-24657964; COSMIC: COSV61968735;