11-19055571-T-C

Position:

• chr11-19055571-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_054030.4(MRGPRX2):​c.832A>G​(p.Ile278Val) 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. 12/21 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: MRGPRX2 NM_054030.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

Genes affected

MRGPRX2 (HGNC:17983): (MAS related GPR family member X2) Enables G protein-coupled receptor activity and neuropeptide binding activity. Involved in mast cell degranulation and positive regulation of cytokinesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37343085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX2	NM_054030.4	c.832A>G	p.Ile278Val	missense_variant	2/2	ENST00000329773.3	NP_473371.1
MRGPRX2	NM_001303615.2	c.832A>G	p.Ile278Val	missense_variant	3/3		NP_001290544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX2	ENST00000329773.3	c.832A>G	p.Ile278Val	missense_variant	2/2	1	NM_054030.4	ENSP00000333800.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.832A>G (p.I278V) alteration is located in exon 2 (coding exon 1) of the MRGPRX2 gene. This alteration results from a A to G substitution at nucleotide position 832, causing the isoleucine (I) at amino acid position 278 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0025	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.20
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.045	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.69		Loss of MoRF binding (P = 0.1412);
MVP		0.52
MPC		0.51
ClinPred		0.92	D
GERP RS		1.6
Varity_R		0.12
gMVP		0.25

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-19077118;