chr2-230910500-G-A

Position:

• chr2-230910500-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005683.4(GPR55):​c.463C>T​(p.Pro155Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR55 NM_005683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR55	NM_005683.4	c.463C>T	p.Pro155Ser	missense_variant	2/2	ENST00000650999.1	NP_005674.2
GPR55	XM_005246952.5	c.463C>T	p.Pro155Ser	missense_variant	2/2		XP_005247009.1
GPR55	XM_011512175.4	c.463C>T	p.Pro155Ser	missense_variant	2/2		XP_011510477.1
GPR55	XM_011512176.3	c.463C>T	p.Pro155Ser	missense_variant	2/2		XP_011510478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR55	ENST00000650999.1	c.463C>T	p.Pro155Ser	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

Feb 13, 2024

The c.463C>T (p.P155S) alteration is located in exon 2 (coding exon 1) of the GPR55 gene. This alteration results from a C to T substitution at nucleotide position 463, causing the proline (P) at amino acid position 155 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	.;T;.;T
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.94	D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	.;N;N;D
REVEL	Benign	0.26
Sift	Benign	0.26	.;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.81	P;P;P;.
Vest4		0.16
MutPred		0.87		Gain of catalytic residue at P155 (P = 0.0136);Gain of catalytic residue at P155 (P = 0.0136);Gain of catalytic residue at P155 (P = 0.0136);Gain of catalytic residue at P155 (P = 0.0136);
MVP		0.84
MPC		0.74
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.22

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: chr2-231775215;