Genetic Variant FCER2:p.Glu231Gln (chr19-7690196-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001220500.2(FCER2):c.691G>C(p.Glu231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

FCER2
NM_001220500.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.077090114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2 link	c.691G>C	p.Glu231Gln	missense_variant	Exon 10 of 11	ENST00000597921.6	NP_001207429.1	P06734
FCER2	NM_002002.5 link	c.691G>C	p.Glu231Gln	missense_variant	Exon 10 of 11		NP_001993.2	P06734
FCER2	NM_001207019.3 link	c.688G>C	p.Glu230Gln	missense_variant	Exon 9 of 10		NP_001193948.2	P06734K3W4U1
FCER2	XM_005272462.5 link	c.691G>C	p.Glu231Gln	missense_variant	Exon 10 of 11		XP_005272519.1	P06734

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6 link	c.691G>C	p.Glu231Gln	missense_variant	Exon 10 of 11	1	NM_001220500.2	ENSP00000471974.1		P06734

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251390

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000133

AC:

194

AN:

1461646

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000168

AC:

187

AN:

1111802

Other (OTH)

AF:

0.0000662

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

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

Feb 27, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.691G>C (p.E231Q) alteration is located in exon 10 (coding exon 9) of the FCER2 gene. This alteration results from a G to C substitution at nucleotide position 691, causing the glutamic acid (E) at amino acid position 231 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.025

.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.54

T;.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.077

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

.;N;N

PhyloP100

-0.061

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.014

Sift

Benign

0.18

T;T;.

Sift4G

Benign

0.085

T;T;T

Polyphen

0.19

.;B;B

Vest4

0.12

MVP

0.26

MPC

0.081

ClinPred

0.034

GERP RS

1.1

Varity_R

0.29

gMVP

0.34

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-7690196-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over