rs2230597

Positions:

chr1-16138178-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004431.5(EPHA2):c.987C>T(p.Pro329Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,608,510 control chromosomes in the GnomAD database, including 127,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11255 hom., cov: 33)

Exomes 𝑓: 0.39 ( 115778 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.511

Variant links:

Genes affected

EPHA2 (HGNC:3386): (EPH receptor A2) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]

EPHA2 links:

EPHA2 (HGNC:):

EPHA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-16138178-G-A is Benign according to our data. Variant chr1-16138178-G-A is described in ClinVar as [Benign]. Clinvar id is 259398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.511 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA2	NM_004431.5 linkuse as main transcript	c.987C>T	p.Pro329Pro	synonymous_variant	5/17	ENST00000358432.8	NP_004422.2	P29317-1A0A024QZA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8 linkuse as main transcript	c.987C>T	p.Pro329Pro	synonymous_variant	5/17	1	NM_004431.5	ENSP00000351209.5		P29317-1
EPHA2	ENST00000480202.1 linkuse as main transcript	n.192C>T		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57538

AN:

151990

Hom.:

11246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.405

GnomAD3 exomes

AF:

0.377

AC:

91745

AN:

243348

Hom.:

18087

AF XY:

0.386

AC XY:

51151

AN XY:

132562

show subpopulations

Gnomad AFR exome

AF:

0.351

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.394

AC:

573757

AN:

1456402

Hom.:

115778

Cov.:

AF XY:

0.397

AC XY:

287863

AN XY:

724632

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.362

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.342

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.394

GnomAD4 genome

AF:

0.378

AC:

57569

AN:

152108

Hom.:

11255

Cov.:

AF XY:

0.377

AC XY:

28068

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.450

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.404

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.403

Hom.:

13026

Bravo

AF:

0.375

Asia WGS

AF:

0.325

AC:

1130

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 6 multiple types

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 01, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.1

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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