19-7689336-G-C

Variant names:

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

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.823C>G​(p.Arg275Gly) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.075142175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.823C>G	p.Arg275Gly	missense_variant	Exon 11 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.823C>G	p.Arg275Gly	missense_variant	Exon 11 of 11		NP_001993.2
FCER2	NM_001207019.3	c.820C>G	p.Arg274Gly	missense_variant	Exon 10 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.823C>G	p.Arg275Gly	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>G	p.Arg275Gly	missense_variant	Exon 11 of 11	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.45
DEOGEN2	Benign	0.015	.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.62	T;.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.51	.;N;N
PhyloP100		0.35
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.32	N;N;.
REVEL	Benign	0.025
Sift	Benign	0.43	T;T;.
Sift4G	Benign	0.20	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.066
MutPred		0.53		.;Loss of solvent accessibility (P = 0.002);Loss of solvent accessibility (P = 0.002);
MVP		0.29
MPC		0.094
ClinPred		0.028	T
GERP RS		1.3
Varity_R		0.40
gMVP		0.37
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;