Genetic Variant EFNB2:p.Ala157Thr (chr13-106495778-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_004093.4(EFNB2):c.469G>A(p.Ala157Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

EFNB2
NM_004093.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

EFNB2 (HGNC:3227): (ephrin B2) This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNB class ephrin which binds to the EPHB4 and EPHA3 receptors. [provided by RefSeq, Jul 2008]

EFNB2 links:

ENSG00000284966 (HGNC:):

ENSG00000284966 links:

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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=0.23745254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFNB2	NM_004093.4 link	c.469G>A	p.Ala157Thr	missense_variant	Exon 3 of 5	ENST00000646441.1	NP_004084.1	P52799
EFNB2	NM_001372057.1 link	c.469G>A	p.Ala157Thr	missense_variant	Exon 3 of 4		NP_001358986.1
EFNB2	XM_017020406.3 link	c.475G>A	p.Ala159Thr	missense_variant	Exon 3 of 5		XP_016875895.1
EFNB2	NM_001372056.1 link	c.407-784G>A		intron_variant	Intron 2 of 3		NP_001358985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFNB2	ENST00000646441.1 link	c.469G>A	p.Ala157Thr	missense_variant	Exon 3 of 5		NM_004093.4	ENSP00000493716.1		P52799

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.469G>A (p.A157T) alteration is located in exon 3 (coding exon 3) of the EFNB2 gene. This alteration results from a G to A substitution at nucleotide position 469, causing the alanine (A) at amino acid position 157 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

Benign

0.086

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.39

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.20

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.22

Sift

Benign

0.52

T;.

Sift4G

Benign

0.41

T;.

Polyphen

0.0

B;B

Vest4

0.18

MutPred

0.35

Loss of MoRF binding (P = 0.1037);Loss of MoRF binding (P = 0.1037);

MVP

0.35

MPC

0.60

ClinPred

0.82

GERP RS

5.5

Varity_R

0.41

gMVP

0.59

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