2-84822041-C-T

Position:

chr2-84822041-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001277053.2(TRABD2A):c.1394G>A(p.Arg465Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,591,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

TRABD2A
NM_001277053.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.91

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015446931).

BP6

Variant 2-84822041-C-T is Benign according to our data. Variant chr2-84822041-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2364012.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRABD2A	NM_001277053.2 linkuse as main transcript	c.1394G>A	p.Arg465Gln	missense_variant	7/7	ENST00000409520.7	NP_001263982.1
TRABD2A	NM_001080824.3 linkuse as main transcript	c.1247G>A	p.Arg416Gln	missense_variant	6/6		NP_001074293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRABD2A	ENST00000409520.7 linkuse as main transcript	c.1394G>A	p.Arg465Gln	missense_variant	7/7	1	NM_001277053.2	ENSP00000387075.2	Q86V40-1
TRABD2A	ENST00000335459.9 linkuse as main transcript	c.1247G>A	p.Arg416Gln	missense_variant	6/6	1		ENSP00000335004.5	Q86V40-2
TRABD2A	ENST00000479944.5 linkuse as main transcript	n.3520G>A		non_coding_transcript_exon_variant	4/4	5
TRABD2A	ENST00000496500.5 linkuse as main transcript	n.739G>A		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000190

AC:

AN:

210944

Hom.:

AF XY:

0.0000265

AC XY:

AN XY:

113306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000131

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000257

AC:

AN:

1438894

Hom.:

Cov.:

AF XY:

0.0000210

AC XY:

AN XY:

713328

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000103

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000908

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.096

DANN

Benign

0.50

DEOGEN2

Benign

0.0011

.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;N

PrimateAI

Benign

0.18

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.0010

Sift

Benign

0.52

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0020

B;B

Vest4

0.086

MutPred

0.20

.;Loss of MoRF binding (P = 0.052);

MVP

0.014

MPC

0.27

ClinPred

0.013

GERP RS

-8.5

Varity_R

0.014

gMVP

0.11

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