20-36878049-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080628.3(TLDC2):​c.184C>G​(p.Arg62Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R62W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLDC2 NM_080628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLDC2	NM_080628.3	c.184C>G	p.Arg62Gly	missense_variant	Exon 2 of 7	ENST00000217320.8	NP_542195.1
TLDC2	XM_017027674.2	c.-100C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5		XP_016883163.1
TLDC2	NM_001304783.1	c.184C>G	p.Arg62Gly	missense_variant	Exon 2 of 6		NP_001291712.1
TLDC2	XM_017027674.2	c.-100C>G		5_prime_UTR_variant	Exon 1 of 5		XP_016883163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLDC2	ENST00000217320.8	c.184C>G	p.Arg62Gly	missense_variant	Exon 2 of 7	1	NM_080628.3	ENSP00000217320.3
TLDC2	ENST00000602922.5	c.184C>G	p.Arg62Gly	missense_variant	Exon 2 of 6	1		ENSP00000473323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248852 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134520

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.066	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	.;N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.046	D;D
Polyphen		0.11	B;B
Vest4		0.57
MutPred		0.48		Gain of catalytic residue at I61 (P = 0.1034);Gain of catalytic residue at I61 (P = 0.1034);
MVP		0.24
MPC		0.061
ClinPred		0.57	D
GERP RS		2.5
Varity_R		0.15
gMVP		0.31

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: -22

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

Publications

LitVar

Other links and lift over

dbSNP: rs184539554; hg19: chr20-35506452;