1-51356840-A-G

Position:

• chr1-51356840-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001981.3(EPS15):​c.2551T>C​(p.Ser851Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: EPS15 NM_001981.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

Genes affected

EPS15 (HGNC:3419): (epidermal growth factor receptor pathway substrate 15) This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]

EPS15 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23333141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS15	NM_001981.3	c.2551T>C	p.Ser851Pro	missense_variant	25/25	ENST00000371733.8	NP_001972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS15	ENST00000371733.8	c.2551T>C	p.Ser851Pro	missense_variant	25/25	1	NM_001981.3	ENSP00000360798.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Aug 11, 2022

The c.2551T>C (p.S851P) alteration is located in exon 25 (coding exon 25) of the EPS15 gene. This alteration results from a T to C substitution at nucleotide position 2551, causing the serine (S) at amino acid position 851 to be replaced by a proline (P). 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	0.67
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	.;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.14
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.97	D;D
Vest4		0.19
MutPred		0.080		.;Gain of catalytic residue at P850 (P = 0.0174);
MVP		0.62
MPC		0.60
ClinPred		0.93	D
GERP RS		4.7
Varity_R		0.64
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-51822512;