9-136671978-A-G

Variant summary

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

The NM_016215.5(EGFL7):​c.689A>G​(p.Glu230Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

EGFL7
NM_016215.5 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93
Variant links:
Genes affected
EGFL7 (HGNC:20594): (EGF like domain multiple 7) This gene encodes a secreted endothelial cell protein that contains two epidermal growth factor-like domains. The encoded protein may play a role in regulating vasculogenesis. This protein may be involved in the growth and proliferation of tumor cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EGFL7NM_016215.5 linkuse as main transcriptc.689A>G p.Glu230Gly missense_variant 10/11 ENST00000308874.12 NP_057299.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EGFL7ENST00000308874.12 linkuse as main transcriptc.689A>G p.Glu230Gly missense_variant 10/111 NM_016215.5 ENSP00000307843 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2023The c.689A>G (p.E230G) alteration is located in exon 10 (coding exon 7) of the EGFL7 gene. This alteration results from a A to G substitution at nucleotide position 689, causing the glutamic acid (E) at amino acid position 230 to be replaced by a glycine (G). 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
Benign
0.093
BayesDel_addAF
Uncertain
0.090
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T;T;T;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.35
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.72
.;T;.;.
M_CAP
Pathogenic
0.32
D
MetaRNN
Uncertain
0.46
T;T;T;T
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Uncertain
2.2
M;M;M;M
MutationTaster
Benign
0.97
D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-2.3
N;N;N;N
REVEL
Uncertain
0.42
Sift
Uncertain
0.0070
D;D;D;D
Sift4G
Uncertain
0.026
D;D;D;D
Polyphen
0.98
D;D;D;D
Vest4
0.32
MutPred
0.20
Loss of stability (P = 0.0587);Loss of stability (P = 0.0587);Loss of stability (P = 0.0587);Loss of stability (P = 0.0587);
MVP
0.97
MPC
0.22
ClinPred
0.80
D
GERP RS
3.0
Varity_R
0.087
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1845938778; hg19: chr9-139566430; API