12-15621360-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004447.6(EPS8):c.2426G>A(p.Ser809Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
EPS8
NM_004447.6 missense
NM_004447.6 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.28
Genes affected
EPS8 (HGNC:3420): (EGFR pathway substrate 8, signaling adaptor) This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
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=0.19319314).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.2426G>A (p.S809N) alteration is located in exon 21 (coding exon 20) of the EPS8 gene. This alteration results from a G to A substitution at nucleotide position 2426, causing the serine (S) at amino acid position 809 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;T;T;T;T;.;T;T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;.;.;D;.;.;.;.;D;.;D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;.;N;N;N;N;.;N;N;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.;.;.;.;.;.;.;.;N;N;N
REVEL
Benign
Sift
Benign
D;.;D;.;.;.;.;.;.;.;.;D;D;D
Sift4G
Benign
T;.;T;.;.;.;.;.;.;.;.;T;T;T
Polyphen
P;P;P;P;.;P;P;P;P;.;P;P;.;.
Vest4
MutPred
Loss of phosphorylation at S809 (P = 0.0053);Loss of phosphorylation at S809 (P = 0.0053);Loss of phosphorylation at S809 (P = 0.0053);Loss of phosphorylation at S809 (P = 0.0053);.;Loss of phosphorylation at S809 (P = 0.0053);Loss of phosphorylation at S809 (P = 0.0053);Loss of phosphorylation at S809 (P = 0.0053);Loss of phosphorylation at S809 (P = 0.0053);.;Loss of phosphorylation at S809 (P = 0.0053);Loss of phosphorylation at S809 (P = 0.0053);.;.;
MVP
MPC
0.29
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.