rs715827

Positions:

• chr3-10270089-A-G

Variant summary

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

The NM_014760.4(TATDN2):​c.949-42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,563,092 control chromosomes in the GnomAD database, including 40,813 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 0.20 (4448 hom., cov: 32)
  • Exomes 𝑓: 0.19 (36365 hom.)
• Consequence: TATDN2 NM_014760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

Genes affected

TATDN2 (HGNC:28988): (TatD DNase domain containing 2) Predicted to enable metal ion binding activity and nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TATDN2	NM_014760.4	c.949-42A>G		intron_variant		ENST00000448281.7	NP_055575.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TATDN2	ENST00000448281.7	c.949-42A>G		intron_variant		1	NM_014760.4	ENSP00000408736	P1
TATDN2	ENST00000287652.8	c.949-42A>G		intron_variant		1		ENSP00000287652	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31144 AN: 152006 Hom.: 4445 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.289 AC: 60788 AN: 210360 Hom.: 13105 AF XY: 0.281 AC XY: 31434 AN XY: 111846

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.698

Gnomad SAS exome AF: 0.431

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.189 AC: 266258 AN: 1410968 Hom.: 36365 Cov.: 32 AF XY: 0.193 AC XY: 134509 AN XY: 696448

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.679

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.205 AC: 31151 AN: 152124 Hom.: 4448 Cov.: 32 AF XY: 0.217 AC XY: 16137 AN XY: 74376

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.191

Alfa AF: 0.182 Hom.: 3092

Bravo AF: 0.217

Asia WGS AF: 0.509 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.021
DANN	Benign	0.51

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: rs715827; hg19: chr3-10311773; COSMIC: COSV55054718; COSMIC: COSV55054718;