19-7689398-C-A

Variant names:

• chr19-7689398-C-A
• rs35825847
• NM_001220500.2:c.761G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001220500.2(FCER2):​c.761G>T​(p.Ser254Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• 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: 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=0.17158437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.761G>T	p.Ser254Ile	missense_variant	Exon 11 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.761G>T	p.Ser254Ile	missense_variant	Exon 11 of 11		NP_001993.2
FCER2	NM_001207019.3	c.758G>T	p.Ser253Ile	missense_variant	Exon 10 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.761G>T	p.Ser254Ile	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.761G>T	p.Ser254Ile	missense_variant	Exon 11 of 11	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449984 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720076

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33232

American (AMR) AF: 0.0000461 AC: 2 AN: 43424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39270

South Asian (SAS) AF: 0.00 AC: 0 AN: 85062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4812

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106238

Other (OTH) AF: 0.00 AC: 0 AN: 59730

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.4
DANN	Benign	0.75
DEOGEN2	Benign	0.035	.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.55	T;.;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.19	.;N;N
PhyloP100		-1.4
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N;N;.
REVEL	Benign	0.017
Sift	Uncertain	0.0030	D;T;.
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.20	.;B;B
Vest4		0.067
MutPred		0.63		.;Loss of disorder (P = 0.0057);Loss of disorder (P = 0.0057);
MVP		0.25
MPC		0.20
ClinPred		0.19	T
GERP RS		-2.8
Varity_R		0.24
gMVP		0.31
Mutation Taster		=88/12	polymorphism

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: rs35825847; hg19: chr19-7754284;