1-16148631-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004431.5(EPHA2):c.570G>A(p.Ala190Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,607,538 control chromosomes in the GnomAD database, including 86,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6607 hom., cov: 33)

Exomes 𝑓: 0.32 ( 80147 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.73

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

cataract 6 multiple types
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
early-onset non-syndromic cataract
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset posterior polar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset posterior subcapsular cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EPHA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-16148631-C-T is Benign according to our data. Variant chr1-16148631-C-T is described in ClinVar as Benign. ClinVar VariationId is 259393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA2	NM_004431.5 link	c.570G>A	p.Ala190Ala	synonymous_variant	Exon 3 of 17	ENST00000358432.8	NP_004422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8 link	c.570G>A	p.Ala190Ala	synonymous_variant	Exon 3 of 17	1	NM_004431.5	ENSP00000351209.5
EPHA2	ENST00000461614.1 link	n.622G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42291

AN:

151930

Hom.:

6599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.320

GnomAD2 exomes

AF:

0.298

AC:

73497

AN:

246464

AF XY:

0.306

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.0176

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.324

AC:

472198

AN:

1455490

Hom.:

80147

Cov.:

AF XY:

0.326

AC XY:

236450

AN XY:

724346

show subpopulations

African (AFR)

AF:

0.166

AC:

5566

AN:

33478

American (AMR)

AF:

0.331

AC:

14785

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

10512

AN:

26134

East Asian (EAS)

AF:

0.0238

AC:

944

AN:

39700

South Asian (SAS)

AF:

0.338

AC:

29159

AN:

86246

European-Finnish (FIN)

AF:

0.278

AC:

13128

AN:

47292

Middle Eastern (MID)

AF:

0.450

AC:

2595

AN:

5768

European-Non Finnish (NFE)

AF:

0.339

AC:

376365

AN:

1111844

Other (OTH)

AF:

0.317

AC:

19144

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

23370

46740

70109

93479

116849

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11954

23908

35862

47816

59770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.278

AC:

42310

AN:

152048

Hom.:

6607

Cov.:

AF XY:

0.277

AC XY:

20608

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.165

AC:

6857

AN:

41516

American (AMR)

AF:

0.346

AC:

5278

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1394

AN:

3464

East Asian (EAS)

AF:

0.0239

AC:

124

AN:

5188

South Asian (SAS)

AF:

0.328

AC:

1581

AN:

4826

European-Finnish (FIN)

AF:

0.274

AC:

2892

AN:

10562

Middle Eastern (MID)

AF:

0.462

AC:

135

AN:

292

European-Non Finnish (NFE)

AF:

0.340

AC:

23069

AN:

67914

Other (OTH)

AF:

0.322

AC:

680

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1556

3113

4669

6226

7782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.294

Hom.:

3737

Bravo

AF:

0.274

Asia WGS

AF:

0.192

AC:

668

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

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 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. -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 01, 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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.56

CADD

Benign

1.2

(source)

DANN

Benign

0.89

PhyloP100

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over