Variant 20-36879145-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_080628.3(TLDC2):c.294G>C(p.Glu98Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 1,614,052 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 30 hom. )

Consequence

TLDC2
NM_080628.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.18

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007662058).

BP6

Variant 20-36879145-G-C is Benign according to our data. Variant chr20-36879145-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2652302.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLDC2	NM_080628.3 linkuse as main transcript	c.294G>C	p.Glu98Asp	missense_variant	3/7	ENST00000217320.8
TLDC2	NM_001304783.1 linkuse as main transcript	c.294G>C	p.Glu98Asp	missense_variant	3/6
TLDC2	XM_017027674.2 linkuse as main transcript	c.6G>C	p.Glu2Asp	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLDC2	ENST00000217320.8 linkuse as main transcript	c.294G>C	p.Glu98Asp	missense_variant	3/7	1	NM_080628.3	P1
TLDC2	ENST00000602922.5 linkuse as main transcript	c.294G>C	p.Glu98Asp	missense_variant	3/6	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

464

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00531

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00274

AC:

688

AN:

251174

Hom.:

AF XY:

0.00267

AC XY:

363

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.00456

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00479

AC:

6995

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

3433

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.00578

Gnomad4 OTH exome

AF:

0.00404

GnomAD4 genome

AF:

0.00305

AC:

464

AN:

152308

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00531

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00475

Hom.:

Bravo

AF:

0.00266

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00282

AC:

343

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00456

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

TLDC2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0033

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

0.83

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.85

.;N

REVEL

Benign

0.041

Sift

Benign

0.23

.;T

Sift4G

Benign

0.45

T;T

Polyphen

0.46

P;P

Vest4

0.28

MutPred

0.34

Gain of phosphorylation at Y94 (P = 0.164);Gain of phosphorylation at Y94 (P = 0.164);

MVP

0.29

MPC

0.053

ClinPred

0.012

GERP RS

0.78

Varity_R

0.13

gMVP

0.22

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