Variant 19-7690243-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000597921.6(FCER2):c.644G>C(p.Ser215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

FCER2
ENST00000597921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.281

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:

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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=0.078528196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FCER2	NM_001220500.2 linkuse as main transcript	c.644G>C	p.Ser215Thr	missense_variant	10/11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5 linkuse as main transcript	c.644G>C	p.Ser215Thr	missense_variant	10/11		NP_001993.2
FCER2	NM_001207019.3 linkuse as main transcript	c.641G>C	p.Ser214Thr	missense_variant	9/10		NP_001193948.2
FCER2	XM_005272462.5 linkuse as main transcript	c.644G>C	p.Ser215Thr	missense_variant	10/11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6 linkuse as main transcript	c.644G>C	p.Ser215Thr	missense_variant	10/11	1	NM_001220500.2	ENSP00000471974	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251302

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135810

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 SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

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

Mar 25, 2024

The c.644G>C (p.S215T) 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 644, causing the serine (S) at amino acid position 215 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.2

DANN

Benign

0.36

DEOGEN2

Benign

0.034

.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.32

T;.;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

N;N;.

REVEL

Benign

0.012

Sift

Uncertain

0.012

D;D;.

Sift4G

Benign

0.23

T;T;T

Polyphen

0.014

.;B;B

Vest4

0.15

MutPred

0.41

.;Loss of disorder (P = 0.0826);Loss of disorder (P = 0.0826);

MVP

0.28

MPC

0.070

ClinPred

0.026

GERP RS

0.089

Varity_R

0.24

gMVP

0.28

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