chr2-230910379-C-T

Variant names:

• chr2-230910379-C-T
• rs3749073
• NM_005683.4:c.584G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005683.4(GPR55):​c.584G>A​(p.Gly195Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.8e-7 (0 hom.)
• Consequence: GPR55 NM_005683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 0 publications found

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]

ENSG00000230385 (HGNC:40260):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118961275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR55	NM_005683.4	c.584G>A	p.Gly195Asp	missense_variant	Exon 2 of 2	ENST00000650999.1	NP_005674.2
GPR55	XM_005246952.5	c.584G>A	p.Gly195Asp	missense_variant	Exon 2 of 2		XP_005247009.1
GPR55	XM_011512175.4	c.584G>A	p.Gly195Asp	missense_variant	Exon 2 of 2		XP_011510477.1
GPR55	XM_011512176.3	c.584G>A	p.Gly195Asp	missense_variant	Exon 2 of 2		XP_011510478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR55	ENST00000650999.1	c.584G>A	p.Gly195Asp	missense_variant	Exon 2 of 2		NM_005683.4	ENSP00000498258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461766 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.25	T;T;T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.70	.;T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PhyloP100		0.020
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	.;N;N;N
REVEL	Benign	0.082
Sift	Benign	0.043	.;D;D;T
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		0.41	B;B;B;.
Vest4		0.32
MutPred		0.45		Loss of catalytic residue at G195 (P = 0.081);Loss of catalytic residue at G195 (P = 0.081);Loss of catalytic residue at G195 (P = 0.081);Loss of catalytic residue at G195 (P = 0.081);
MVP		0.31
MPC		0.46
ClinPred		0.14	T
GERP RS		-0.72
Varity_R		0.47
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs3749073; hg19: chr2-231775094;