dbSNP rs76826147: EPHB2:p.Lys1019Gln (chr1-22913757-A-C) – 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_001309193.2(EPHB2):c.3055A>C(p.Lys1019Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EPHB2
NM_001309193.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.261

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 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=0.0795497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5 link	c.*187A>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000374630.8	NP_059145.2	P29323-2Q6NVW1Q4LE53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPHB2	ENST00000400191.7 link	c.3055A>C	p.Lys1019Gln	missense_variant	Exon 17 of 17	1		ENSP00000383053.3	P29323-1
EPHB2	ENST00000374630.8 link	c.*187A>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_017449.5	ENSP00000363761.3	P29323-2
EPHB2	ENST00000374632.7 link	c.*187A>C		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000363763.3	P29323-3
EPHB2	ENST00000374627.1 link	c.*1154A>C		downstream_gene_variant		5		ENSP00000363758.1	B1AKC9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722618

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.3

DANN

Benign

0.91

DEOGEN2

Benign

0.075

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

PROVEAN

Benign

0.010

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.13

MutPred

0.12

Loss of methylation at K1019 (P = 0.0152);

MVP

0.67

ClinPred

0.096

GERP RS

0.90

Varity_R

0.15

gMVP

0.046

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

Computational scores

Splicing

Publications

Other links and lift over