rs56043737

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000358432.8(EPHA2):c.1941G>T(p.Thr647=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,854 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T647T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.012 ( 28 hom., cov: 33)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

EPHA2
ENST00000358432.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.87

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=-0.56).

BP6

Variant 1-16133292-C-A is Benign according to our data. Variant chr1-16133292-C-A is described in ClinVar as [Benign]. Clinvar id is 293418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16133292-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-5.87 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0115 (1756/152216) while in subpopulation AMR AF= 0.0233 (357/15302). AF 95% confidence interval is 0.0213. There are 28 homozygotes in gnomad4. There are 909 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1756 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA2	NM_004431.5 linkuse as main transcript	c.1941G>T	p.Thr647=	synonymous_variant	11/17	ENST00000358432.8	NP_004422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8 linkuse as main transcript	c.1941G>T	p.Thr647=	synonymous_variant	11/17	1	NM_004431.5	ENSP00000351209	P1	P29317-1
EPHA2	ENST00000462805.1 linkuse as main transcript	n.159G>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1757

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0234

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.0229

GnomAD3 exomes

AF:

0.0111

AC:

2793

AN:

251252

Hom.:

AF XY:

0.0113

AC XY:

1539

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.00944

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0124

AC:

18086

AN:

1461638

Hom.:

130

Cov.:

AF XY:

0.0123

AC XY:

8947

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.00930

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.0202

Gnomad4 NFE exome

AF:

0.0137

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0115

AC:

1756

AN:

152216

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

909

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0160

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	EPHA2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 12, 2018	- -

Cataract 6 multiple types

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.34

DANN

Benign

0.77

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