chr11-19055679-G-T

Position:

• chr11-19055679-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_054030.4(MRGPRX2):​c.724C>A​(p.Gln242Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: MRGPRX2 NM_054030.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08780211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRX2	NM_054030.4	c.724C>A	p.Gln242Lys	missense_variant	2/2	ENST00000329773.3	NP_473371.1
MRGPRX2	NM_001303615.2	c.724C>A	p.Gln242Lys	missense_variant	3/3		NP_001290544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRX2	ENST00000329773.3	c.724C>A	p.Gln242Lys	missense_variant	2/2	1	NM_054030.4	ENSP00000333800.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Nov 27, 2024

The c.724C>A (p.Q242K) alteration is located in exon 2 (coding exon 1) of the MRGPRX2 gene. This alteration results from a C to A substitution at nucleotide position 724, causing the glutamine (Q) at amino acid position 242 to be replaced by a lysine (K). 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	0.16
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.020
DANN	Benign	0.44
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.012	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.16
Sift	Benign	0.12	T
Sift4G	Benign	0.20	T
Polyphen		0.029	B
Vest4		0.082
MutPred		0.73		Gain of ubiquitination at Q242 (P = 0.0369);
MVP		0.30
MPC		0.15
ClinPred		0.15	T
GERP RS		-10
Varity_R		0.074
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs1849608127; hg19: chr11-19077226;