Variant 20-36889299-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_080628.3(TLDC2):c.561C>A(p.Ser187Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 1,614,178 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts 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: 0.0047 ( 30 hom. )

Consequence

TLDC2
NM_080628.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.208

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06825146).

BP6

Variant 20-36889299-C-A is Benign according to our data. Variant chr20-36889299-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652303.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.561C>A	p.Ser187Arg	missense_variant	6/7	ENST00000217320.8
TLDC2	NM_001304783.1 linkuse as main transcript	c.465C>A	p.Ser155Arg	missense_variant	5/6
TLDC2	XM_017027674.2 linkuse as main transcript	c.273C>A	p.Ser91Arg	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TLDC2	ENST00000217320.8 linkuse as main transcript	c.561C>A	p.Ser187Arg	missense_variant	6/7	1	NM_080628.3	P1
TLDC2	ENST00000602922.5 linkuse as main transcript	c.561C>A	p.Ser187Arg	missense_variant	6/6	1		P1
TLDC2	ENST00000436941.1 linkuse as main transcript	c.74+1771C>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152202

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:

0.00104

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00271

AC:

680

AN:

251310

Hom.:

AF XY:

0.00264

AC XY:

359

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00117

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:

0.00157

Gnomad NFE exome

AF:

0.00451

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00475

AC:

6938

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

3406

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.00573

Gnomad4 OTH exome

AF:

0.00392

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152320

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74482

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:

0.00526

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00445

Hom.:

Bravo

AF:

0.00266

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00281

AC:

341

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00450

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

Pathogenic

0.99

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T

Eigen

Uncertain

0.40

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Pathogenic

3.8

H;H

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.5

.;D

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.89

MutPred

0.81

Gain of solvent accessibility (P = 0.0365);Gain of solvent accessibility (P = 0.0365);

MVP

0.71

MPC

0.35

ClinPred

0.11

GERP RS

3.5

Varity_R

0.95

gMVP

0.82

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