19-7689335-C-T

Variant names:

• chr19-7689335-C-T
• rs145983387
• NM_001220500.2:c.824G>A

Variant summary

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

The NM_001220500.2(FCER2):​c.824G>A​(p.Arg275His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,612,592 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R275C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0740
• Publications: 0 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=0.027450025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.824G>A	p.Arg275His	missense_variant	Exon 11 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.824G>A	p.Arg275His	missense_variant	Exon 11 of 11		NP_001993.2
FCER2	NM_001207019.3	c.821G>A	p.Arg274His	missense_variant	Exon 10 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.824G>A	p.Arg275His	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.824G>A	p.Arg275His	missense_variant	Exon 11 of 11	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000574 AC: 14 AN: 244014 AF XY: 0.0000602

Gnomad AFR exome AF: 0.000390

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000221

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1460280 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 726450

African (AFR) AF: 0.000448 AC: 15 AN: 33460

American (AMR) AF: 0.0000898 AC: 4 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111542

Other (OTH) AF: 0.00 AC: 0 AN: 60228

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74472

African (AFR) AF: 0.000457 AC: 19 AN: 41562

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000151

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000495 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.824G>A (p.R275H) alteration is located in exon 11 (coding exon 10) of the FCER2 gene. This alteration results from a G to A substitution at nucleotide position 824, causing the arginine (R) at amino acid position 275 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.015	.;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.81	T;.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.027	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	.;L;L
PhyloP100		-0.074
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.19	N;N;.
REVEL	Benign	0.050
Sift	Benign	0.58	T;T;.
Sift4G	Benign	0.082	T;T;T
Polyphen		0.67	.;P;P
Vest4		0.043
MVP		0.31
MPC		0.10
ClinPred		0.025	T
GERP RS		1.6
Varity_R		0.30
gMVP		0.27
Mutation Taster		=94/6	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: rs145983387; hg19: chr19-7754221;