20-36887791-A-T

Position:

• chr20-36887791-A-T

Variant summary

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

The NM_080628.3(TLDC2):​c.512+263A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,120 control chromosomes in the GnomAD database, including 44,611 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 0.76 (44611 hom., cov: 32)
• Consequence: TLDC2 NM_080628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978

Genes affected

TLDC2 (HGNC:16112): (TBC/LysM-associated domain containing 2) Predicted to be involved in response to oxidative stress. Predicted to act upstream of or within negative regulation of oxidative stress-induced neuron death. Predicted to be active in nucleus. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLDC2	NM_080628.3	c.512+263A>T		intron_variant		ENST00000217320.8	NP_542195.1
TLDC2	NM_001304783.1	c.416+263A>T		intron_variant			NP_001291712.1
TLDC2	XM_017027674.2	c.224+263A>T		intron_variant			XP_016883163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLDC2	ENST00000217320.8	c.512+263A>T		intron_variant		1	NM_080628.3	ENSP00000217320.3
TLDC2	ENST00000602922.5	c.512+263A>T		intron_variant		1		ENSP00000473323.1
TLDC2	ENST00000436941.1	c.74+263A>T		intron_variant		3		ENSP00000394804.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115080 AN: 152002 Hom.: 44584 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.780

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.757 AC: 115150 AN: 152120 Hom.: 44611 Cov.: 32 AF XY: 0.754 AC XY: 56075 AN XY: 74382

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.780

Alfa AF: 0.752 Hom.: 2431

Bravo AF: 0.739

Asia WGS AF: 0.696 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1291139; hg19: chr20-35516194;