rs184539554

Variant names:

• chr20-36878049-C-A
• rs184539554
• NM_080628.3:c.184C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-36878049-C-A
• chr20-36878049-C-G
• chr20-36878049-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080628.3(TLDC2):​c.184C>A​(p.Arg62Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,272 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: 6.8e-7 (0 hom.)
• Consequence: TLDC2 NM_080628.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080628.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLDC2	NM_080628.3	MANE Select	c.184C>A	p.Arg62Arg	synonymous	Exon 2 of 7	NP_542195.1	A0PJX2
	TLDC2	NM_001304783.1		c.184C>A	p.Arg62Arg	synonymous	Exon 2 of 6	NP_001291712.1	A0PJX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLDC2	ENST00000217320.8	TSL:1 MANE Select	c.184C>A	p.Arg62Arg	synonymous	Exon 2 of 7	ENSP00000217320.3	A0PJX2
	TLDC2	ENST00000602922.5	TSL:1	c.184C>A	p.Arg62Arg	synonymous	Exon 2 of 6	ENSP00000473323.1	A0PJX2
	TLDC2	ENST00000866646.1		c.184C>A	p.Arg62Arg	synonymous	Exon 2 of 7	ENSP00000536705.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248852 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460272 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726396

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111190

Other (OTH) AF: 0.00 AC: 0 AN: 60312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.46
PhyloP100		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs184539554; hg19: chr20-35506452;