chr1-37719558-C-G

Position:

• chr1-37719558-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001099439.2(EPHA10):​c.2612G>C​(p.Cys871Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPHA10 NM_001099439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

Genes affected

EPHA10 (HGNC:19987): (EPH receptor A10) Ephrin receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility in neuronal and epithelial cells (Aasheim et al., 2005 [PubMed 15777695]). See MIM 179610 for additional background on Eph receptors and ephrins.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA10	NM_001099439.2	c.2612G>C	p.Cys871Ser	missense_variant	15/17	ENST00000373048.9	NP_001092909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA10	ENST00000373048.9	c.2612G>C	p.Cys871Ser	missense_variant	15/17	5	NM_001099439.2	ENSP00000362139.4
EPHA10	ENST00000432874.7	n.*506G>C		non_coding_transcript_exon_variant	10/16	5		ENSP00000436425.1
EPHA10	ENST00000432874.7	n.*506G>C		3_prime_UTR_variant	10/16	5		ENSP00000436425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.2612G>C (p.C871S) alteration is located in exon 15 (coding exon 15) of the EPHA10 gene. This alteration results from a G to C substitution at nucleotide position 2612, causing the cysteine (C) at amino acid position 871 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-9.2	D;D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.94
MutPred		0.89		Gain of disorder (P = 0.0052);Gain of disorder (P = 0.0052);
MVP		0.95
MPC		0.60
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.95
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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: chr1-38185230;