chr9-136671978-A-G

Position:

• chr9-136671978-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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93

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]

ACMG classification

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
EGFL7	NM_016215.5	c.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
EGFL7	ENST00000308874.12	c.689A>G	p.Glu230Gly	missense_variant	10/11	1	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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The 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

Other links and lift over

dbSNP: rs1845938778; hg19: chr9-139566430;