rs10907223

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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=-0.59).

BP6

Variant 1-16133250-G-A is Benign according to our data. Variant chr1-16133250-G-A is described in ClinVar as [Benign]. Clinvar id is 259389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16133250-G-A is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA2	NM_004431.5 linkuse as main transcript	c.1983C>T	p.Leu661Leu	synonymous_variant	11/17	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.1983C>T	p.Leu661Leu	synonymous_variant	11/17	1	NM_004431.5	ENSP00000351209.5		P29317-1
EPHA2	ENST00000462805.1 linkuse as main transcript	n.201C>T		non_coding_transcript_exon_variant	2/2	3

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

GnomAD3 exomes

AF:

0.0842

AC:

21151

AN:

251182

Hom.:

1983

AF XY:

0.0776

AC XY:

10532

AN XY:

135790

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 SAS exome

AF:

0.0989

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

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.0829

Gnomad4 ASJ exome

AF:

0.0584

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.0970

Gnomad4 FIN exome

AF:

0.0510

Gnomad4 NFE exome

AF:

0.0333

Gnomad4 OTH exome

AF:

0.0736

GnomAD4 genome

AF:

0.150

AC:

22865

AN:

152088

Hom.:

3722

Cov.:

AF XY:

0.150

AC XY:

11184

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.0881

Gnomad4 ASJ

AF:

0.0648

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.0974

Gnomad4 FIN

AF:

0.0579

Gnomad4 NFE

AF:

0.0340

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.0652

Hom.:

1308

Bravo

AF:

0.167

Asia WGS

AF:

0.163

AC:

566

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 6 multiple types

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 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

-0.59

CADD

Benign

2.6

DANN

Benign

0.82

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