chr1-16125272-G-A

Variant names:

Variant summary

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

The NM_004431.5(EPHA2):c.2874C>T(p.Ile958Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,613,100 control chromosomes in the GnomAD database, including 62,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4945 hom., cov: 31)

Exomes 𝑓: 0.28 ( 57407 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.42

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:

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=-0.47).

BP6

Variant 1-16125272-G-A is Benign according to our data. Variant chr1-16125272-G-A is described in ClinVar as [Benign]. Clinvar id is 259392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16125272-G-A is described in Lovd as [Benign]. Variant chr1-16125272-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA2	NM_004431.5 link	c.2874C>T	p.Ile958Ile	synonymous_variant	Exon 17 of 17	ENST00000358432.8	NP_004422.2	P29317-1A0A024QZA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8 link	c.2874C>T	p.Ile958Ile	synonymous_variant	Exon 17 of 17	1	NM_004431.5	ENSP00000351209.5		P29317-1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36763

AN:

151750

Hom.:

4943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.278

AC:

69557

AN:

250116

Hom.:

10305

AF XY:

0.285

AC XY:

38649

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.276

AC:

403401

AN:

1461232

Hom.:

57407

Cov.:

AF XY:

0.280

AC XY:

203228

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.354

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.242

AC:

36771

AN:

151868

Hom.:

4945

Cov.:

AF XY:

0.246

AC XY:

18288

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.273

Hom.:

12518

Bravo

AF:

0.238

Asia WGS

AF:

0.294

AC:

1024

AN:

3476

EpiCase

AF:

0.293

EpiControl

AF:

0.298

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

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.0

DANN

Benign

0.83

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

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