rs34753465

Positions:

Variant summary

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

The NM_004431.5(EPHA2):c.648C>T(p.Ala216Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0078 in 1,613,028 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 21 hom., cov: 33)

Exomes 𝑓: 0.0078 ( 107 hom. )

Consequence

EPHA2
NM_004431.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.71

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=-0.81).

BP6

Variant 1-16148553-G-A is Benign according to our data. Variant chr1-16148553-G-A is described in ClinVar as [Benign]. Clinvar id is 259395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-16148553-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.71 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00773 (1178/152398) while in subpopulation AMR AF= 0.0362 (554/15312). AF 95% confidence interval is 0.0337. There are 21 homozygotes in gnomad4. There are 609 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA2	NM_004431.5 linkuse as main transcript	c.648C>T	p.Ala216Ala	synonymous_variant	3/17	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.648C>T	p.Ala216Ala	synonymous_variant	3/17	1	NM_004431.5	ENSP00000351209.5		P29317-1
EPHA2	ENST00000461614.1 linkuse as main transcript	n.700C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

1179

AN:

152280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00730

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.0114

AC:

2845

AN:

250122

Hom.:

AF XY:

0.00988

AC XY:

1337

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.0552

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.000482

Gnomad NFE exome

AF:

0.00645

Gnomad OTH exome

AF:

0.00819

GnomAD4 exome

AF:

0.00781

AC:

11408

AN:

1460630

Hom.:

107

Cov.:

AF XY:

0.00748

AC XY:

5435

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.0513

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00336

Gnomad4 FIN exome

AF:

0.000690

Gnomad4 NFE exome

AF:

0.00745

Gnomad4 OTH exome

AF:

0.00624

GnomAD4 genome

AF:

0.00773

AC:

1178

AN:

152398

Hom.:

Cov.:

AF XY:

0.00817

AC XY:

609

AN XY:

74530

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.0362

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00730

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00637

Hom.:

Bravo

AF:

0.00951

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00616

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cataract 6 multiple types

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
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. -

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

-0.81

CADD

Benign

0.51

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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