Variant chr19-7689347-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001220500.2(FCER2):c.812C>A(p.Ala271Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FCER2
NM_001220500.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FCER2	NM_001220500.2 linkuse as main transcript	c.812C>A	p.Ala271Asp	missense_variant	11/11	ENST00000597921.6
FCER2	NM_002002.5 linkuse as main transcript	c.812C>A	p.Ala271Asp	missense_variant	11/11
FCER2	NM_001207019.3 linkuse as main transcript	c.809C>A	p.Ala270Asp	missense_variant	10/10
FCER2	XM_005272462.5 linkuse as main transcript	c.812C>A	p.Ala271Asp	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER2	ENST00000597921.6 linkuse as main transcript	c.812C>A	p.Ala271Asp	missense_variant	11/11	1	NM_001220500.2	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

241972

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131846

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000925

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726040

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

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

Apr 04, 2023

The c.812C>A (p.A271D) alteration is located in exon 11 (coding exon 10) of the FCER2 gene. This alteration results from a C to A substitution at nucleotide position 812, causing the alanine (A) at amino acid position 271 to be replaced by an aspartic acid (D). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.16

.;T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.59

T;.;T

M_CAP

Benign

0.0054

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L;L

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.7

D;D;.

REVEL

Benign

0.14

Sift

Benign

0.94

T;D;.

Sift4G

Uncertain

0.044

D;D;D

Polyphen

0.99

.;D;D

Vest4

0.46

MVP

0.45

MPC

0.14

ClinPred

0.37

GERP RS

2.8

Varity_R

0.70

gMVP

0.55

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