Genetic Variant NM_004431.5:c.823+33delG (chr1-16148344-AC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004431.5(EPHA2):c.823+33delG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12955 hom., cov: 0)

Exomes 𝑓: 0.38 ( 108428 hom. )

Consequence

EPHA2
NM_004431.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.28

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 -10 ACMG points.

BP6

Variant 1-16148344-AC-A is Benign according to our data. Variant chr1-16148344-AC-A is described in ClinVar as [Benign]. Clinvar id is 1177896.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA2	NM_004431.5 link	c.823+33delG		intron_variant	Intron 3 of 16	ENST00000358432.8	NP_004422.2	P29317-1A0A024QZA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8 link	c.823+33delG		intron_variant	Intron 3 of 16	1	NM_004431.5	ENSP00000351209.5		P29317-1
EPHA2	ENST00000461614.1 link	n.*33delG		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61196

AN:

151860

Hom.:

12932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.0711

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.364

AC:

90667

AN:

249310

Hom.:

17707

AF XY:

0.367

AC XY:

49625

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.367

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.0688

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.379

AC:

553141

AN:

1459280

Hom.:

108428

Cov.:

AF XY:

0.380

AC XY:

275835

AN XY:

726070

show subpopulations

Gnomad4 AFR exome

AF:

0.497

Gnomad4 AMR exome

AF:

0.368

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.0728

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.403

AC:

61271

AN:

151978

Hom.:

12955

Cov.:

AF XY:

0.399

AC XY:

29618

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.490

Gnomad4 AMR

AF:

0.410

Gnomad4 ASJ

AF:

0.488

Gnomad4 EAS

AF:

0.0712

Gnomad4 SAS

AF:

0.373

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.421

Alfa

AF:

0.403

Hom.:

2292

Bravo

AF:

0.408

Asia WGS

AF:

0.251

AC:

873

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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