19-7690507-A-G

Variant names:

• chr19-7690507-A-G
• rs1400063852
• NM_001220500.2:c.520T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001220500.2(FCER2):​c.520T>C​(p.Cys174Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. C174S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.520T>C	p.Cys174Arg	missense_variant	Exon 9 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.520T>C	p.Cys174Arg	missense_variant	Exon 9 of 11		NP_001993.2
FCER2	NM_001207019.3	c.517T>C	p.Cys173Arg	missense_variant	Exon 8 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.520T>C	p.Cys174Arg	missense_variant	Exon 9 of 11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6	c.520T>C	p.Cys174Arg	missense_variant	Exon 9 of 11	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251344 AF XY: 0.00

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: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520T>C (p.C174R) alteration is located in exon 9 (coding exon 8) of the FCER2 gene. This alteration results from a T to C substitution at nucleotide position 520, causing the cysteine (C) at amino acid position 174 to be replaced by an arginine (R). 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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	.;D;D;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.68	T;.;T;T
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.97	D;D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.7	.;H;H;.
PhyloP100		2.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-12	D;D;.;.
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.72
MutPred		0.91		.;Gain of MoRF binding (P = 0.0247);Gain of MoRF binding (P = 0.0247);.;
MVP		0.55
MPC		0.54
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.98
gMVP		0.92
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1400063852; hg19: chr19-7755393;