Variant rs6669624 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004431.5(EPHA2):c.1738+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,541,078 control chromosomes in the GnomAD database, including 13,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 5783 hom., cov: 33)

Exomes 𝑓: 0.074 ( 7593 hom. )

Consequence

EPHA2
NM_004431.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.44

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 1-16133844-G-A is Benign according to our data. Variant chr1-16133844-G-A is described in ClinVar as [Benign]. Clinvar id is 259388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHA2	NM_004431.5 linkuse as main transcript	c.1738+16C>T		intron_variant		ENST00000358432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA2	ENST00000358432.8 linkuse as main transcript	c.1738+16C>T		intron_variant		1	NM_004431.5	P1	P29317-1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29399

AN:

152044

Hom.:

5766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0808

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0953

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0582

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.106

AC:

15965

AN:

149950

Hom.:

1706

AF XY:

0.0981

AC XY:

7701

AN XY:

78476

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.0906

Gnomad ASJ exome

AF:

0.0694

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.0934

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0983

GnomAD4 exome

AF:

0.0743

AC:

103140

AN:

1388916

Hom.:

7593

Cov.:

AF XY:

0.0739

AC XY:

50505

AN XY:

683644

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.0974

Gnomad4 ASJ exome

AF:

0.0726

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.0906

Gnomad4 NFE exome

AF:

0.0547

Gnomad4 OTH exome

AF:

0.0983

GnomAD4 genome

AF:

0.194

AC:

29458

AN:

152162

Hom.:

5783

Cov.:

AF XY:

0.193

AC XY:

14369

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.503

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.0808

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0953

Gnomad4 NFE

AF:

0.0581

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.119

Hom.:

496

Bravo

AF:

0.211

Asia WGS

AF:

0.176

AC:

613

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cataract 6 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.28

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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