2-230910220-A-T

Position:

• chr2-230910220-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005683.4(GPR55):​c.743T>A​(p.Leu248Gln) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR55 NM_005683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.28

Genes affected

GPR55 (HGNC:4511): (G protein-coupled receptor 55) This gene belongs to the G-protein-coupled receptor superfamily. The encoded integral membrane protein is a likely cannabinoid receptor. It may be involved in several physiological and pathological processes by activating a variety of signal transduction pathways. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR55	NM_005683.4	c.743T>A	p.Leu248Gln	missense_variant	2/2	ENST00000650999.1	NP_005674.2
GPR55	XM_005246952.5	c.743T>A	p.Leu248Gln	missense_variant	2/2		XP_005247009.1
GPR55	XM_011512175.4	c.743T>A	p.Leu248Gln	missense_variant	2/2		XP_011510477.1
GPR55	XM_011512176.3	c.743T>A	p.Leu248Gln	missense_variant	2/2		XP_011510478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR55	ENST00000650999.1	c.743T>A	p.Leu248Gln	missense_variant	2/2		NM_005683.4	ENSP00000498258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Dec 10, 2024

The c.743T>A (p.L248Q) alteration is located in exon 2 (coding exon 1) of the GPR55 gene. This alteration results from a T to A substitution at nucleotide position 743, causing the leucine (L) at amino acid position 248 to be replaced by a glutamine (Q). 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	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.78	.;T;.
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.5	M;M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.9	.;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.92
MutPred		0.61		Gain of catalytic residue at L248 (P = 0.01);Gain of catalytic residue at L248 (P = 0.01);Gain of catalytic residue at L248 (P = 0.01);
MVP		0.71
MPC		0.95
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-231774935;