Variant chr2-84839152-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000409520.7(TRABD2A):c.988G>A(p.Ala330Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRABD2A
ENST00000409520.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRABD2A	NM_001277053.2 linkuse as main transcript	c.988G>A	p.Ala330Thr	missense_variant	4/7	ENST00000409520.7	NP_001263982.1
TRABD2A	NM_001080824.3 linkuse as main transcript	c.841G>A	p.Ala281Thr	missense_variant	3/6		NP_001074293.1
TRABD2A	NM_001307978.2 linkuse as main transcript	c.988G>A	p.Ala330Thr	missense_variant	4/5		NP_001294907.1
TRABD2A	XM_047443257.1 linkuse as main transcript	c.841G>A	p.Ala281Thr	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.988G>A	p.Ala330Thr	missense_variant	4/7	1	NM_001277053.2	ENSP00000387075	P1	Q86V40-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461620

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Aug 28, 2023

The c.841G>A (p.A281T) alteration is located in exon 3 (coding exon 3) of the TRABD2A gene. This alteration results from a G to A substitution at nucleotide position 841, causing the alanine (A) at amino acid position 281 to be replaced by a threonine (T). 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.97

D;D;T

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.1

.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.017

D;D;D

Sift4G

Benign

0.067

T;T;D

Polyphen

1.0

D;P;D

Vest4

0.77

MutPred

0.81

.;Gain of phosphorylation at A330 (P = 0.1582);Gain of phosphorylation at A330 (P = 0.1582);

MVP

0.32

MPC

0.86

ClinPred

0.98

GERP RS

2.9

Varity_R

0.18

gMVP

0.81

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over