Variant 19-7689359-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000597921.6(FCER2):c.800G>C(p.Arg267Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,610,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

FCER2
ENST00000597921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.283

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05064997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FCER2	NM_001220500.2 linkuse as main transcript	c.800G>C	p.Arg267Pro	missense_variant	11/11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5 linkuse as main transcript	c.800G>C	p.Arg267Pro	missense_variant	11/11		NP_001993.2
FCER2	NM_001207019.3 linkuse as main transcript	c.797G>C	p.Arg266Pro	missense_variant	10/10		NP_001193948.2
FCER2	XM_005272462.5 linkuse as main transcript	c.800G>C	p.Arg267Pro	missense_variant	11/11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6 linkuse as main transcript	c.800G>C	p.Arg267Pro	missense_variant	11/11	1	NM_001220500.2	ENSP00000471974	P2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152182

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:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000885

AC:

AN:

237404

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

129614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000847

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000946

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000288

AC:

AN:

1458056

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

725192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000505

Gnomad4 SAS exome

AF:

0.000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000578

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Jun 05, 2023

The c.800G>C (p.R267P) alteration is located in exon 11 (coding exon 10) of the FCER2 gene. This alteration results from a G to C substitution at nucleotide position 800, causing the arginine (R) at amino acid position 267 to be replaced by a proline (P). 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

0.71

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.068

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.26

T;.;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.91

.;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.032

Sift

Benign

0.061

T;T;.

Sift4G

Benign

0.20

T;T;T

Polyphen

0.055

.;B;B

Vest4

0.16

MutPred

0.63

.;Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);

MVP

0.22

MPC

0.18

ClinPred

0.018

GERP RS

-1.6

Varity_R

0.83

gMVP

0.64

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