Genetic Variant FCER2:p.Gln153Pro (chr19-7696836-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001220500.2(FCER2):c.458A>C(p.Gln153Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,425,846 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: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

FCER2
NM_001220500.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0470

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.089395285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2 link	c.458A>C	p.Gln153Pro	missense_variant	Exon 8 of 11	ENST00000597921.6	NP_001207429.1	P06734
FCER2	NM_002002.5 link	c.458A>C	p.Gln153Pro	missense_variant	Exon 8 of 11		NP_001993.2	P06734
FCER2	NM_001207019.3 link	c.455A>C	p.Gln152Pro	missense_variant	Exon 7 of 10		NP_001193948.2	P06734K3W4U1
FCER2	XM_005272462.5 link	c.458A>C	p.Gln153Pro	missense_variant	Exon 8 of 11		XP_005272519.1	P06734

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6 link	c.458A>C	p.Gln153Pro	missense_variant	Exon 8 of 11	1	NM_001220500.2	ENSP00000471974.1		P06734

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000511

AC:

AN:

195870

AF XY:

0.00000961

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:

0.0000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1425846

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

705494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32994

American (AMR)

AF:

0.00

AC:

AN:

39086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25464

East Asian (EAS)

AF:

0.00

AC:

AN:

38376

South Asian (SAS)

AF:

0.00

AC:

AN:

81300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00000275

AC:

AN:

1092876

Other (OTH)

AF:

0.0000169

AC:

AN:

59102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 05, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.458A>C (p.Q153P) alteration is located in exon 8 (coding exon 7) of the FCER2 gene. This alteration results from a A to C substitution at nucleotide position 458, causing the glutamine (Q) at amino acid position 153 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

Benign

0.30

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.29

.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.41

T;.;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.089

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;N;.

PhyloP100

0.047

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.3

N;N;.;.

REVEL

Benign

0.052

Sift

Benign

0.087

T;T;.;.

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.65

.;P;P;.

Vest4

0.29

MutPred

0.46

.;Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);.;

MVP

0.33

MPC

0.18

ClinPred

0.15

GERP RS

-4.6

Varity_R

0.19

gMVP

0.61

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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19-7696836-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over