2-230910427-G-A

Position:

• chr2-230910427-G-A

Variant summary

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

The NM_005683.4(GPR55):​c.536C>T​(p.Ala179Val) 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. 15/20 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)
• Consequence: GPR55 NM_005683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06816056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR55	NM_005683.4	c.536C>T	p.Ala179Val	missense_variant	2/2	ENST00000650999.1	NP_005674.2
GPR55	XM_005246952.5	c.536C>T	p.Ala179Val	missense_variant	2/2		XP_005247009.1
GPR55	XM_011512175.4	c.536C>T	p.Ala179Val	missense_variant	2/2		XP_011510477.1
GPR55	XM_011512176.3	c.536C>T	p.Ala179Val	missense_variant	2/2		XP_011510478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR55	ENST00000650999.1	c.536C>T	p.Ala179Val	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

Sep 10, 2024

The c.536C>T (p.A179V) 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 536, causing the alanine (A) at amino acid position 179 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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.57
DEOGEN2	Benign	0.017	T;T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.64	.;T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.25	.;N;N;N
REVEL	Benign	0.055
Sift	Benign	0.87	.;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0030	B;B;B;.
Vest4		0.055
MutPred		0.45		Gain of methylation at K180 (P = 0.0387);Gain of methylation at K180 (P = 0.0387);Gain of methylation at K180 (P = 0.0387);Gain of methylation at K180 (P = 0.0387);
MVP		0.34
MPC		0.27
ClinPred		0.10	T
GERP RS		4.3
Varity_R		0.072

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: chr2-231775142;