rs2230598

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.2034A>G(p.Leu678Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 1,613,644 control chromosomes in the GnomAD database, including 520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 262 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 258 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.501

Publications

2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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=-0.62).

BP6

Variant 1-16133199-T-C is Benign according to our data. Variant chr1-16133199-T-C is described in ClinVar as Benign. ClinVar VariationId is 293415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.501 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004431.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA2	NM_004431.5	MANE Select	c.2034A>G	p.Leu678Leu	synonymous	Exon 11 of 17	NP_004422.2
	EPHA2	NM_001329090.2		c.1872A>G	p.Leu624Leu	synonymous	Exon 10 of 16	NP_001316019.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPHA2	ENST00000358432.8	TSL:1 MANE Select	c.2034A>G	p.Leu678Leu	synonymous	Exon 11 of 17	ENSP00000351209.5	P29317-1
EPHA2	ENST00000917106.1		c.2034A>G	p.Leu678Leu	synonymous	Exon 11 of 17	ENSP00000587165.1
EPHA2	ENST00000863593.1		c.2034A>G	p.Leu678Leu	synonymous	Exon 11 of 17	ENSP00000533652.1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5031

AN:

152042

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.00894

AC:

2242

AN:

250906

AF XY:

0.00642

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.00721

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00342

AC:

4999

AN:

1461484

Hom.:

258

Cov.:

AF XY:

0.00293

AC XY:

2130

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.116

AC:

3892

AN:

33476

American (AMR)

AF:

0.00857

AC:

383

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000174

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53170

Middle Eastern (MID)

AF:

0.00434

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000172

AC:

191

AN:

1111916

Other (OTH)

AF:

0.00817

AC:

493

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

335

670

1004

1339

1674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.0332

AC:

5052

AN:

152160

Hom.:

262

Cov.:

AF XY:

0.0322

AC XY:

2396

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.113

AC:

4705

AN:

41460

American (AMR)

AF:

0.0171

AC:

261

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

67964

Other (OTH)

AF:

0.0260

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

226

451

677

902

1128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0183

Hom.:

Bravo

AF:

0.0379

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 6 multiple types (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.5

(source)

DANN

Benign

0.85

PhyloP100

0.50

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over