rs3087584

Variant names:

• chr2-221418561-T-A
• rs3087584
• NM_004438.5:c.*2811A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-221418561-T-A
• chr2-221418561-T-C
• chr2-221418561-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004438.5(EPHA4):​c.*2811A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EPHA4 NM_004438.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 5 publications found

Genes affected

EPHA4 (HGNC:3388): (EPH receptor A4) 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

EPHA4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA4	NM_004438.5	c.*2811A>T		3_prime_UTR_variant	Exon 18 of 18	ENST00000281821.7	NP_004429.1
EPHA4	NM_001304536.2	c.*2811A>T		3_prime_UTR_variant	Exon 19 of 19		NP_001291465.1
EPHA4	NM_001363748.2	c.*2951A>T		3_prime_UTR_variant	Exon 18 of 18		NP_001350677.1
EPHA4	NM_001304537.2	c.*2811A>T		3_prime_UTR_variant	Exon 17 of 17		NP_001291466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA4	ENST00000281821.7	c.*2811A>T		3_prime_UTR_variant	Exon 18 of 18	1	NM_004438.5	ENSP00000281821.2
EPHA4	ENST00000469354.1	n.2359A>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 17442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.38

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

Other links and lift over

dbSNP: rs3087584; hg19: chr2-222283281;