rs28936395

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017449.5(EPHB2):c.2032G>A(p.Asp678Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00535 in 1,614,172 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D678E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 31 hom. )

Consequence

EPHB2
NM_017449.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

EPHB2 (HGNC:3393): (EPH receptor B2) This gene encodes a member of the Eph receptor family of receptor tyrosine kinase transmembrane glycoproteins. These receptors are composed of an N-terminal glycosylated ligand-binding domain, a transmembrane region and an intracellular kinase domain. They bind ligands called ephrins and are involved in diverse cellular processes including motility, division, and differentiation. A distinguishing characteristic of Eph-ephrin signaling is that both receptors and ligands are competent to transduce a signaling cascade, resulting in bidirectional signaling. This protein belongs to a subgroup of the Eph receptors called EphB. Proteins of this subgroup are distinguished from other members of the family by sequence homology and preferential binding affinity for membrane-bound ephrin-B ligands. Allelic variants are associated with prostate and brain cancer susceptibility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

EPHB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02323693).

BP6

Variant 1-22906853-G-A is Benign according to our data. Variant chr1-22906853-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 8534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5 link	c.2032G>A	p.Asp678Asn	missense_variant	Exon 11 of 16	ENST00000374630.8	NP_059145.2	P29323-2Q6NVW1Q4LE53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPHB2	ENST00000374630.8 link	c.2032G>A	p.Asp678Asn	missense_variant	Exon 11 of 16	1	NM_017449.5	ENSP00000363761.3	P29323-2
EPHB2	ENST00000400191.7 link	c.2032G>A	p.Asp678Asn	missense_variant	Exon 11 of 17	1		ENSP00000383053.3	P29323-1
EPHB2	ENST00000374632.7 link	c.2035G>A	p.Asp679Asn	missense_variant	Exon 11 of 16	1		ENSP00000363763.3	P29323-3
EPHB2	ENST00000374627.1 link	c.2017G>A	p.Asp673Asn	missense_variant	Exon 11 of 15	5		ENSP00000363758.1	B1AKC9

Frequencies

GnomAD3 genomes

AF:

0.00315

AC:

480

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00554

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00347

AC:

872

AN:

251398

Hom.:

AF XY:

0.00343

AC XY:

466

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00573

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00558

AC:

8163

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

3888

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.00245

Gnomad4 NFE exome

AF:

0.00664

Gnomad4 OTH exome

AF:

0.00531

GnomAD4 genome

AF:

0.00315

AC:

480

AN:

152290

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

220

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00554

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00388

Hom.:

Bravo

AF:

0.00359

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00709

AC:

ExAC

AF:

0.00342

AC:

415

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00551

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Prostate cancer/brain cancer susceptibility

Pathogenic:1Benign:1

Jan 01, 2019

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 01, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

EPHB2-related disorder

Benign:1

May 18, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

.;D;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.023

T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.41

N;N;.;.

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.030

D;D;D;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

1.0, 0.94

.;D;P;.

Vest4

0.61

MVP

0.76

MPC

1.4

ClinPred

0.039

GERP RS

5.4

Varity_R

0.47

gMVP

0.58

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