rs3212231

Positions:

• chr6-24657736-T-C
• chr6-24657736-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016614.3(TDP2):​c.517+76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 644,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000310 AC: 2 AN: 644306 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 337290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000456

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0030
DANN	Benign	0.70

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;