rs10917325

Variant names:

• chr1-22882785-C-T
• rs10917325
• NM_017449.5:c.1428+302C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017449.5(EPHB2):​c.1428+302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 371,658 control chromosomes in the GnomAD database, including 36,093 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (13079 hom., cov: 33)
  • Exomes 𝑓: 0.44 (23014 hom.)
• Consequence: EPHB2 NM_017449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 4 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB2	NM_017449.5	MANE Select	c.1428+302C>T		intron	N/A	NP_059145.2
	EPHB2	NM_001309193.2		c.1428+302C>T		intron	N/A	NP_001296122.1
	EPHB2	NM_004442.7		c.1428+302C>T		intron	N/A	NP_004433.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHB2	ENST00000374630.8	TSL:1 MANE Select	c.1428+302C>T		intron	N/A	ENSP00000363761.3
	EPHB2	ENST00000400191.7	TSL:1	c.1428+302C>T		intron	N/A	ENSP00000383053.3
	EPHB2	ENST00000374632.7	TSL:1	c.1428+302C>T		intron	N/A	ENSP00000363763.3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56605 AN: 152062 Hom.: 13075 Cov.: 33

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.401

GnomAD4 exome AF: 0.441 AC: 96782 AN: 219478 Hom.: 23014 Cov.: 3 AF XY: 0.421 AC XY: 49756 AN XY: 118066

African (AFR) AF: 0.0917 AC: 567 AN: 6180

American (AMR) AF: 0.534 AC: 6057 AN: 11338

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 2570 AN: 5444

East Asian (EAS) AF: 0.323 AC: 3182 AN: 9860

South Asian (SAS) AF: 0.267 AC: 10741 AN: 40158

European-Finnish (FIN) AF: 0.502 AC: 5169 AN: 10304

Middle Eastern (MID) AF: 0.346 AC: 269 AN: 778

European-Non Finnish (NFE) AF: 0.509 AC: 63159 AN: 124196

Other (OTH) AF: 0.452 AC: 5068 AN: 11220

GnomAD4 genome AF: 0.372 AC: 56613 AN: 152180 Hom.: 13079 Cov.: 33 AF XY: 0.370 AC XY: 27512 AN XY: 74402

African (AFR) AF: 0.0953 AC: 3961 AN: 41554

American (AMR) AF: 0.485 AC: 7409 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3472

East Asian (EAS) AF: 0.313 AC: 1618 AN: 5168

South Asian (SAS) AF: 0.259 AC: 1250 AN: 4822

European-Finnish (FIN) AF: 0.481 AC: 5097 AN: 10590

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34308 AN: 67972

Other (OTH) AF: 0.400 AC: 843 AN: 2110

Alfa AF: 0.449 Hom.: 2695

Bravo AF: 0.365

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.6
DANN	Benign	0.82
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10917325; hg19: chr1-23209278; COSMIC: COSV65861001;