rs28936395

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

bleeding disorder, platelet-type, 22
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

EPHB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 8534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017449.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EPHB2	NM_017449.5	MANE Select	c.2032G>A	p.Asp678Asn	missense	Exon 11 of 16	NP_059145.2
EPHB2	NM_001309193.2		c.2032G>A	p.Asp678Asn	missense	Exon 11 of 17	NP_001296122.1
EPHB2	NM_004442.7		c.2035G>A	p.Asp679Asn	missense	Exon 11 of 16	NP_004433.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EPHB2	ENST00000374630.8	TSL:1 MANE Select	c.2032G>A	p.Asp678Asn	missense	Exon 11 of 16	ENSP00000363761.3
EPHB2	ENST00000400191.7	TSL:1	c.2032G>A	p.Asp678Asn	missense	Exon 11 of 17	ENSP00000383053.3
EPHB2	ENST00000374632.7	TSL:1	c.2035G>A	p.Asp679Asn	missense	Exon 11 of 16	ENSP00000363763.3

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

GnomAD2 exomes

AF:

0.00347

AC:

872

AN:

251398

AF XY:

0.00343

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 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

African (AFR)

AF:

0.00105

AC:

AN:

33480

American (AMR)

AF:

0.00215

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00147

AC:

127

AN:

86252

European-Finnish (FIN)

AF:

0.00245

AC:

131

AN:

53414

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00664

AC:

7383

AN:

1112012

Other (OTH)

AF:

0.00531

AC:

321

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

543

1085

1628

2170

2713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00315

AC:

480

AN:

152290

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

220

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41554

American (AMR)

AF:

0.00222

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00554

AC:

377

AN:

68022

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00431

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

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Prostate cancer/brain cancer susceptibility (2)

EPHB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.023

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.41

PhyloP100

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.33

Sift

Benign

0.030

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.61

MVP

0.76

MPC

1.4

ClinPred

0.039

GERP RS

5.4

Varity_R

0.47

gMVP

0.58

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over