19-7689222-G-A

Variant names:

• chr19-7689222-G-A
• NM_001220500.2:c.937C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001220500.2(FCER2):​c.937C>T​(p.Pro313Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.134
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06705749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.937C>T	p.Pro313Ser	missense_variant	Exon 11 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.937C>T	p.Pro313Ser	missense_variant	Exon 11 of 11		NP_001993.2
FCER2	NM_001207019.3	c.934C>T	p.Pro312Ser	missense_variant	Exon 10 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.937C>T	p.Pro313Ser	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.937C>T	p.Pro313Ser	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.937C>T (p.P313S) alteration is located in exon 11 (coding exon 10) of the FCER2 gene. This alteration results from a C to T substitution at nucleotide position 937, causing the proline (P) at amino acid position 313 to be replaced by a serine (S). 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	0.083
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.7
DANN	Benign	0.91
DEOGEN2	Benign	0.017	.;T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.46	T;.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	.;N;N
PhyloP100		0.13
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.45	N;N;.
REVEL	Benign	0.035
Sift	Benign	0.56	T;T;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.75	.;P;P
Vest4		0.066
MVP		0.30
MPC		0.078
ClinPred		0.081	T
GERP RS		-0.92
Varity_R		0.027
gMVP		0.41
Mutation Taster		=99/1	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

hg19: chr19-7754108;