1-16148344-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004431.5(EPHA2):c.823+33del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.28

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]

ACMG classification

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/exons	MANE	UniProt
EPHA2	NM_004431.5	c.823+33del		intron_variant		ENST00000358432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA2	ENST00000358432.8	c.823+33del		intron_variant		1	NM_004431.5	P1
EPHA2	ENST00000461614.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61196 AN: 151860 Hom.: 12932 Cov.: 0

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

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.: 0 AF XY: 0.380 AC XY: 275835 AN XY: 726070

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.: 0 AF XY: 0.399 AC XY: 29618 AN XY: 74278

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35127370; hg19: chr1-16474839;