rs377564979

Variant names:

• chr19-7690411-C-G
• rs377564979
• NM_001220500.2:c.616G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-7690411-C-G
• chr19-7690411-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001220500.2(FCER2):​c.616G>C​(p.Glu206Gln) 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. 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. E206K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.616G>C	p.Glu206Gln	missense_variant	Exon 9 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.616G>C	p.Glu206Gln	missense_variant	Exon 9 of 11		NP_001993.2
FCER2	NM_001207019.3	c.613G>C	p.Glu205Gln	missense_variant	Exon 8 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.616G>C	p.Glu206Gln	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.616G>C	p.Glu206Gln	missense_variant	Exon 9 of 11	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.80	T;.;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.9	.;M;M
PhyloP100		2.7
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;.
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.37
MutPred		0.91		.;Loss of phosphorylation at S203 (P = 0.1688);Loss of phosphorylation at S203 (P = 0.1688);
MVP		0.68
MPC		0.29
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.85
gMVP		0.66
Mutation Taster		=68/32	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: rs377564979; hg19: chr19-7755297;