Variant 4-109913149-TTCAGAAGGTCTCTCAGTTGAAGAAAGAGCTTGGAGGACAACAGCACAACAGGAGAGTAAAAGATGCCCCAGGGCTGAGGCCTCCGCTCAGGCAGCCGCATCTGGGGTCAATCATACTCACCTTGCCCGGGCCATGCTCCAGCAAAATCAAGCTGTTTTCTTTTGAAAGTTCAAACTCATCAAGATTATGCTGCTCACTCTTATCATTCTGTTGCCAGTAGTTTCAAAATTTAGTTTTGTTAGTCTCTCAGCACCGCAGCACTGGAGCTGTCC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001963.6(EGF):c.-185_87del variant causes a start lost, 5 prime UTR 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: 32)

Consequence

EGF
NM_001963.6 start_lost, 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.36

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
EGF	NM_001963.6 linkuse as main transcript	c.-185_87del	start_lost, 5_prime_UTR_variant	1/24	ENST00000265171.10
EGF	NM_001178130.3 linkuse as main transcript	c.-185_87del	start_lost, 5_prime_UTR_variant	1/23
EGF	NM_001178131.3 linkuse as main transcript	c.-185_87del	start_lost, 5_prime_UTR_variant	1/23
EGF	NM_001357021.2 linkuse as main transcript	c.-185_87del	start_lost, 5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGF	ENST00000265171.10 linkuse as main transcript	c.-185_87del	start_lost, 5_prime_UTR_variant	1/24	1	NM_001963.6	P1	P01133-1
EGF	ENST00000503392.1 linkuse as main transcript		coding_sequence_variant, 5_prime_UTR_variant	1/23	1			P01133-3
EGF	ENST00000509793.5 linkuse as main transcript	c.-185_87del	start_lost, 5_prime_UTR_variant	1/23	2			P01133-2
EGF	ENST00000652245.1 linkuse as main transcript	c.-185_87del	start_lost, 5_prime_UTR_variant	1/20

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 28, 2023

This sequence change affects the initiator methionine of the EGF mRNA. The next in-frame methionine is located at codon 79. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EGF-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.