Variant 15-90889570-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002005.4(FES):c.860A>G(p.Glu287Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,613,590 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000068 ( 1 hom. )

Consequence

FES
NM_002005.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.33

Variant links:

Genes affected

FES (HGNC:3657): (FES proto-oncogene, tyrosine kinase) This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]

FES links:

FES (HGNC:):

FES links:

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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
FES	NM_002005.4 linkuse as main transcript	c.860A>G	p.Glu287Gly	missense_variant	7/19	ENST00000328850.8	NP_001996.1	P07332-1A0A024RC92

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FES	ENST00000328850.8 linkuse as main transcript	c.860A>G	p.Glu287Gly	missense_variant	7/19	1	NM_002005.4	ENSP00000331504.3		P07332-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251110

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461576

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 01, 2022

The c.860A>G (p.E287G) alteration is located in exon 7 (coding exon 6) of the FES gene. This alteration results from a A to G substitution at nucleotide position 860, causing the glutamic acid (E) at amino acid position 287 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

0.20

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;T;.;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.48

T;T;T;T;T

MetaSVM

Uncertain

0.22

MutationAssessor

Uncertain

2.3

M;.;.;.;M

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.2

D;D;D;D;D

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;D;D

Polyphen

0.57

P;D;D;P;D

Vest4

0.33

MVP

0.92

MPC

0.71

ClinPred

0.97

GERP RS

4.6

Varity_R

0.37

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over