Variant 2-84839301-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001277053.2(TRABD2A):c.839C>T(p.Thr280Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,609,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

TRABD2A
NM_001277053.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

TRABD2A (HGNC:27013): (TraB domain containing 2A) Enables Wnt-protein binding activity and metalloendopeptidase activity. Involved in negative regulation of Wnt signaling pathway and proteolysis. Is integral component of organelle membrane and integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRABD2A links:

TRABD2A (HGNC:):

TRABD2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20337912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRABD2A	NM_001277053.2 linkuse as main transcript	c.839C>T	p.Thr280Met	missense_variant	4/7	ENST00000409520.7	NP_001263982.1
TRABD2A	NM_001080824.3 linkuse as main transcript	c.692C>T	p.Thr231Met	missense_variant	3/6		NP_001074293.1
TRABD2A	NM_001307978.2 linkuse as main transcript	c.839C>T	p.Thr280Met	missense_variant	4/5		NP_001294907.1
TRABD2A	XM_047443257.1 linkuse as main transcript	c.692C>T	p.Thr231Met	missense_variant	3/4		XP_047299213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRABD2A	ENST00000409520.7 linkuse as main transcript	c.839C>T	p.Thr280Met	missense_variant	4/7	1	NM_001277053.2	ENSP00000387075.2		Q86V40-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000454

AC:

AN:

242252

Hom.:

AF XY:

0.0000532

AC XY:

AN XY:

131534

show subpopulations

Gnomad AFR exome

AF:

0.0000658

Gnomad AMR exome

AF:

0.0000903

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.0000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000466

AC:

AN:

1457872

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

725046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000685

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151950

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.692C>T (p.T231M) alteration is located in exon 3 (coding exon 3) of the TRABD2A gene. This alteration results from a C to T substitution at nucleotide position 692, causing the threonine (T) at amino acid position 231 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.089

Sift

Benign

0.030

D;D;D

Sift4G

Benign

0.061

T;D;D

Polyphen

1.0

D;B;D

Vest4

0.41

MutPred

0.48

.;Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);

MVP

0.095

MPC

0.76

ClinPred

0.23

GERP RS

-0.76

Varity_R

0.11

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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