chr1-16133250-G-A

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.1983C>T(p.Leu661Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,613,688 control chromosomes in the GnomAD database, including 8,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 3722 hom., cov: 33)

Exomes 𝑓: 0.053 ( 4949 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.30

Publications

21 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=-0.59).

BP6

Variant 1-16133250-G-A is Benign according to our data. Variant chr1-16133250-G-A is described in ClinVar as Benign. ClinVar VariationId is 259389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 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.1983C>T	p.Leu661Leu	synonymous	Exon 11 of 17	NP_004422.2
	EPHA2	NM_001329090.2		c.1821C>T	p.Leu607Leu	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.1983C>T	p.Leu661Leu	synonymous	Exon 11 of 17	ENSP00000351209.5	P29317-1
EPHA2	ENST00000917106.1		c.1983C>T	p.Leu661Leu	synonymous	Exon 11 of 17	ENSP00000587165.1
EPHA2	ENST00000863593.1		c.1983C>T	p.Leu661Leu	synonymous	Exon 11 of 17	ENSP00000533652.1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22806

AN:

151970

Hom.:

3709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.0648

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0982

Gnomad FIN

AF:

0.0579

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0340

Gnomad OTH

AF:

0.123

GnomAD2 exomes

AF:

0.0842

AC:

21151

AN:

251182

AF XY:

0.0776

show subpopulations

Gnomad AFR exome

AF:

0.416

Gnomad AMR exome

AF:

0.0786

Gnomad ASJ exome

AF:

0.0571

Gnomad EAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0511

Gnomad NFE exome

AF:

0.0383

Gnomad OTH exome

AF:

0.0747

GnomAD4 exome

AF:

0.0526

AC:

76826

AN:

1461600

Hom.:

4949

Cov.:

AF XY:

0.0527

AC XY:

38299

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.421

AC:

14099

AN:

33478

American (AMR)

AF:

0.0829

AC:

3706

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0584

AC:

1524

AN:

26116

East Asian (EAS)

AF:

0.112

AC:

4437

AN:

39700

South Asian (SAS)

AF:

0.0970

AC:

8369

AN:

86258

European-Finnish (FIN)

AF:

0.0510

AC:

2714

AN:

53256

Middle Eastern (MID)

AF:

0.0841

AC:

485

AN:

5766

European-Non Finnish (NFE)

AF:

0.0333

AC:

37047

AN:

1111934

Other (OTH)

AF:

0.0736

AC:

4445

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4966

9932

14899

19865

24831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1688

3376

5064

6752

8440

<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:

0.150

AC:

22865

AN:

152088

Hom.:

3722

Cov.:

AF XY:

0.150

AC XY:

11184

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.407

AC:

16873

AN:

41410

American (AMR)

AF:

0.0881

AC:

1348

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0648

AC:

225

AN:

3472

East Asian (EAS)

AF:

0.117

AC:

607

AN:

5188

South Asian (SAS)

AF:

0.0974

AC:

470

AN:

4824

European-Finnish (FIN)

AF:

0.0579

AC:

615

AN:

10624

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0340

AC:

2310

AN:

67952

Other (OTH)

AF:

0.123

AC:

260

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

795

1591

2386

3182

3977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.0739

Hom.:

1998

Bravo

AF:

0.167

Asia WGS

AF:

0.163

AC:

566

AN:

3478

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)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.6

(source)

DANN

Benign

0.82

PhyloP100

1.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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