Variant 19-7698767-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001220500.2(FCER2):c.110G>A(p.Gly37Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,613,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

FCER2
NM_001220500.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.212

Variant links:

Genes affected

FCER2 (HGNC:3612): (Fc epsilon receptor II) The protein encoded by this gene is a B-cell specific antigen, and a low-affinity receptor for IgE. It has essential roles in B cell growth and differentiation, and the regulation of IgE production. This protein also exists as a soluble secreted form, then functioning as a potent mitogenic growth factor. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

FCER2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12904945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FCER2	NM_001220500.2 linkuse as main transcript	c.110G>A	p.Gly37Glu	missense_variant	3/11	ENST00000597921.6
FCER2	NM_002002.5 linkuse as main transcript	c.110G>A	p.Gly37Glu	missense_variant	3/11
FCER2	NM_001207019.3 linkuse as main transcript	c.107G>A	p.Gly36Glu	missense_variant	2/10
FCER2	XM_005272462.5 linkuse as main transcript	c.110G>A	p.Gly37Glu	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER2	ENST00000597921.6 linkuse as main transcript	c.110G>A	p.Gly37Glu	missense_variant	3/11	1	NM_001220500.2	P2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000645

AC:

AN:

247874

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

134324

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000286

AC:

418

AN:

1460958

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

192

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000367

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000125

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000660

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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

Oct 26, 2022

The c.110G>A (p.G37E) alteration is located in exon 3 (coding exon 2) of the FCER2 gene. This alteration results from a G to A substitution at nucleotide position 110, causing the glycine (G) at amino acid position 37 to be replaced by a glutamic acid (E). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.75

T;.;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.1

N;N;.;.

REVEL

Benign

0.17

Sift

Uncertain

0.020

D;T;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.99

.;D;D;.

Vest4

0.66

MVP

0.63

MPC

0.41

ClinPred

0.10

GERP RS

0.62

Varity_R

0.091

gMVP

0.30

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