Genetic Variant EGF:p.Glu920Gly (chr4-109993271-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001963.6(EGF):c.2759A>G(p.Glu920Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E920V) has been classified as Benign.

Frequency

Genomes: not found (cov: 29)

Consequence

EGF
NM_001963.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

62 publications found

Variant links:

Genes affected

EGF (HGNC:3229): (epidermal growth factor) This gene encodes a member of the epidermal growth factor superfamily. The encoded preproprotein is proteolytically processed to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by binding with high affinity to the cell surface receptor, epidermal growth factor receptor. Defects in this gene are the cause of hypomagnesemia type 4. Dysregulation of this gene has been associated with the growth and progression of certain cancers. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

EGF Gene-Disease associations (from GenCC):

familial primary hypomagnesemia with normocalciuria and normocalcemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
renal hypomagnesemia 4
Inheritance: Unknown, AR, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

EGF links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083471775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001963.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGF	NM_001963.6	MANE Select	c.2759A>G	p.Glu920Gly	missense	Exon 19 of 24	NP_001954.2	P01133-1
EGF	NM_001178131.3		c.2633A>G	p.Glu878Gly	missense	Exon 18 of 23	NP_001171602.1	P01133-2
EGF	NM_001357021.2		c.2390A>G	p.Glu797Gly	missense	Exon 16 of 20	NP_001343950.1	A0A494C018

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGF	ENST00000265171.10	TSL:1 MANE Select	c.2759A>G	p.Glu920Gly	missense	Exon 19 of 24	ENSP00000265171.5	P01133-1
EGF	ENST00000503392.1	TSL:1	c.2735-1462A>G		intron	N/A	ENSP00000421384.1	P01133-3
EGF	ENST00000509996.1	TSL:1	n.444A>G		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

37428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

4.4

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.65

M_CAP

Benign

0.018

MetaRNN

Benign

0.083

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

0.79

PhyloP100

-1.4

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.59

REVEL

Benign

0.082

Sift

Uncertain

0.0010

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.061

MutPred

0.39

Loss of glycosylation at S922 (P = 0.0453)

MVP

0.67

MPC

0.21

ClinPred

0.073

GERP RS

1.3

Varity_R

0.089

gMVP

0.62

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over