chr20-36879155-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_080628.3(TLDC2):c.304G>A(p.Gly102Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,613,948 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0063 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 86 hom. )

Consequence

TLDC2
NM_080628.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.37

Variant links:

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]

TLDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009071469).

BP6

Variant 20-36879155-G-A is Benign according to our data. Variant chr20-36879155-G-A is described in ClinVar as [Benign]. Clinvar id is 782349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00634 (965/152272) while in subpopulation EAS AF= 0.0453 (234/5162). AF 95% confidence interval is 0.0406. There are 19 homozygotes in gnomad4. There are 614 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLDC2	NM_080628.3 link	c.304G>A	p.Gly102Arg	missense_variant	Exon 3 of 7	ENST00000217320.8	NP_542195.1	A0PJX2
TLDC2	NM_001304783.1 link	c.304G>A	p.Gly102Arg	missense_variant	Exon 3 of 6		NP_001291712.1	A0PJX2
TLDC2	XM_017027674.2 link	c.16G>A	p.Gly6Arg	missense_variant	Exon 2 of 5		XP_016883163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLDC2	ENST00000217320.8 link	c.304G>A	p.Gly102Arg	missense_variant	Exon 3 of 7	1	NM_080628.3	ENSP00000217320.3		A0PJX2
TLDC2	ENST00000602922.5 link	c.304G>A	p.Gly102Arg	missense_variant	Exon 3 of 6	1		ENSP00000473323.1		A0PJX2

Frequencies

GnomAD3 genomes

AF:

0.00630

AC:

958

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0450

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0293

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.0104

AC:

2616

AN:

251040

Hom.:

AF XY:

0.00991

AC XY:

1345

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0455

Gnomad SAS exome

AF:

0.00921

Gnomad FIN exome

AF:

0.0279

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00364

AC:

5321

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2773

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.0207

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0320

Gnomad4 SAS exome

AF:

0.00991

Gnomad4 FIN exome

AF:

0.0253

Gnomad4 NFE exome

AF:

0.000439

Gnomad4 OTH exome

AF:

0.00671

GnomAD4 genome

AF:

0.00634

AC:

965

AN:

152272

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

614

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0453

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0293

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00513

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00970

AC:

1178

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 01, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.89

.;D

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.11

.;N

REVEL

Benign

0.14

Sift

Benign

0.035

.;D

Sift4G

Benign

0.071

T;T

Polyphen

0.53

P;P

Vest4

0.40

MutPred

0.24

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MPC

0.11

ClinPred

0.024

GERP RS

4.1

Varity_R

0.20

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over