19-7689336-G-A

Variant names:

• chr19-7689336-G-A
• rs139146098
• NM_001220500.2:c.823C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001220500.2(FCER2):​c.823C>T​(p.Arg275Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,612,484 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R275H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.350
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007913202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.823C>T	p.Arg275Cys	missense_variant	Exon 11 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.823C>T	p.Arg275Cys	missense_variant	Exon 11 of 11		NP_001993.2
FCER2	NM_001207019.3	c.820C>T	p.Arg274Cys	missense_variant	Exon 10 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.823C>T	p.Arg275Cys	missense_variant	Exon 11 of 11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6	c.823C>T	p.Arg275Cys	missense_variant	Exon 11 of 11	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000168 AC: 41 AN: 243400 AF XY: 0.000136

Gnomad AFR exome AF: 0.00196

Gnomad AMR exome AF: 0.000147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000551

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000103 AC: 151 AN: 1460172 Hom.: 1 Cov.: 31 AF XY: 0.000109 AC XY: 79 AN XY: 726368

African (AFR) AF: 0.00284 AC: 95 AN: 33460

American (AMR) AF: 0.000337 AC: 15 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53180

Middle Eastern (MID) AF: 0.00128 AC: 7 AN: 5448

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111520

Other (OTH) AF: 0.000299 AC: 18 AN: 60224

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000577 AC XY: 43 AN XY: 74466

African (AFR) AF: 0.00192 AC: 80 AN: 41570

American (AMR) AF: 0.000392 AC: 6 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000180 Hom.: 0

Bravo AF: 0.000642

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000198 AC: 24

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.823C>T (p.R275C) alteration is located in exon 11 (coding exon 10) of the FCER2 gene. This alteration results from a C to T substitution at nucleotide position 823, causing the arginine (R) at amino acid position 275 to be replaced by a cysteine (C). 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	0.53
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.17	.;T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.85	T;.;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.0079	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;L
PhyloP100		0.35
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.064
Sift	Benign	0.19	T;D;.
Sift4G	Uncertain	0.050	T;D;D
Polyphen		0.98	.;D;D
Vest4		0.18
MVP		0.58
MPC		0.44
ClinPred		0.039	T
GERP RS		1.3
Varity_R		0.23
gMVP		0.43
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs139146098; hg19: chr19-7754222;