chr1-16135086-G-C

Variant names:

• chr1-16135086-G-C
• NM_004431.5:c.1532C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004431.5(EPHA2):​c.1532C>G​(p.Thr511Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T511M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPHA2 NM_004431.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA2	NM_004431.5	c.1532C>G	p.Thr511Arg	missense_variant	Exon 7 of 17	ENST00000358432.8	NP_004422.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHA2	ENST00000358432.8	c.1532C>G	p.Thr511Arg	missense_variant	Exon 7 of 17	1	NM_004431.5	ENSP00000351209.5
EPHA2	ENST00000480202.1	n.737C>G		non_coding_transcript_exon_variant	Exon 5 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.72		Loss of sheet (P = 0.0817);
MVP		0.64
MPC		0.60
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.96
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: 14

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16461581;