1-22784889-G-A

Variant names:

• chr1-22784889-G-A
• rs141122680
• NM_017449.5:c.624G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017449.5(EPHB2):​c.624G>A​(p.Gln208Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,613,776 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (2 hom.)
• Consequence: EPHB2 NM_017449.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620

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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-22784889-G-A is Benign according to our data. Variant chr1-22784889-G-A is described in ClinVar as [Benign]. Clinvar id is 767661.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.062 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB2	NM_017449.5	c.624G>A	p.Gln208Gln	synonymous_variant	Exon 3 of 16	ENST00000374630.8	NP_059145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB2	ENST00000374630.8	c.624G>A	p.Gln208Gln	synonymous_variant	Exon 3 of 16	1	NM_017449.5	ENSP00000363761.3
EPHB2	ENST00000374627.1	c.606G>A	p.Gln202Gln	synonymous_variant	Exon 3 of 15	5		ENSP00000363758.1

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 173 AN: 152266 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000335 AC: 84 AN: 250896 AF XY: 0.000280

Gnomad AFR exome AF: 0.00432

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000146 AC: 214 AN: 1461392 Hom.: 2 Cov.: 32 AF XY: 0.000118 AC XY: 86 AN XY: 726996

Gnomad4 AFR exome AF: 0.00508 AC: 170 AN: 33478

Gnomad4 AMR exome AF: 0.000246 AC: 11 AN: 44718

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26126

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39694

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86246

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53086

Gnomad4 NFE exome AF: 0.00000630 AC: 7 AN: 1111890

Gnomad4 Remaining exome AF: 0.000414 AC: 25 AN: 60386

GnomAD4 genome AF: 0.00114 AC: 173 AN: 152384 Hom.: 1 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74518

Gnomad4 AFR AF: 0.00382 AC: 0.00382193 AN: 0.00382193

Gnomad4 AMR AF: 0.000522 AC: 0.000522466 AN: 0.000522466

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000147 AC: 0.0000146998 AN: 0.0000146998

Gnomad4 OTH AF: 0.00236 AC: 0.00236295 AN: 0.00236295

Alfa AF: 0.000458 Hom.: 0

Bravo AF: 0.00139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.7
DANN	Benign	0.76
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs141122680; hg19: chr1-23111382;