2-84839203-T-C

Position:

• chr2-84839203-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001277053.2(TRABD2A):​c.937A>G​(p.Lys313Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TRABD2A NM_001277053.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62

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 (HGNC:):

ACMG classification

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=0.2425983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRABD2A	NM_001277053.2	c.937A>G	p.Lys313Glu	missense_variant	4/7	ENST00000409520.7	NP_001263982.1
TRABD2A	NM_001080824.3	c.790A>G	p.Lys264Glu	missense_variant	3/6		NP_001074293.1
TRABD2A	NM_001307978.2	c.937A>G	p.Lys313Glu	missense_variant	4/5		NP_001294907.1
TRABD2A	XM_047443257.1	c.790A>G	p.Lys264Glu	missense_variant	3/4		XP_047299213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRABD2A	ENST00000409520.7	c.937A>G	p.Lys313Glu	missense_variant	4/7	1	NM_001277053.2	ENSP00000387075.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.790A>G (p.K264E) alteration is located in exon 3 (coding exon 3) of the TRABD2A gene. This alteration results from a A to G substitution at nucleotide position 790, causing the lysine (K) at amino acid position 264 to be replaced by a glutamic acid (E). 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	0.26
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	.;T;.
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.074
Sift	Benign	0.97	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.96	D;P;B
Vest4		0.57
MutPred		0.42		.;Loss of MoRF binding (P = 0.0088);Loss of MoRF binding (P = 0.0088);
MVP		0.16
MPC		0.97
ClinPred		0.81	D
GERP RS		3.8
Varity_R		0.18
gMVP		0.67

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

Other links and lift over

dbSNP: rs1681621810; hg19: chr2-85066327;