2-174445130-C-T

Variant names:

• chr2-174445130-C-T
• NM_152529.7:c.2060G>A

Variant summary

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

The NM_152529.7(GPR155):​c.2060G>A​(p.Arg687Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPR155 NM_152529.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

Genes affected

GPR155 (HGNC:22951): (G protein-coupled receptor 155) Involved in cognition. Located in extracellular exosome. [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=0.23063666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR155	NM_152529.7	c.2060G>A	p.Arg687Lys	missense_variant	Exon 13 of 16	ENST00000392552.7	NP_689742.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR155	ENST00000392552.7	c.2060G>A	p.Arg687Lys	missense_variant	Exon 13 of 16	1	NM_152529.7	ENSP00000376335.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2060G>A (p.R687K) alteration is located in exon 14 (coding exon 12) of the GPR155 gene. This alteration results from a G to A substitution at nucleotide position 2060, causing the arginine (R) at amino acid position 687 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	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.066	.;T;T;T
Eigen	Benign	-0.092
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;.;.;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M;M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	.;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.89	.;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0050	.;B;B;B
Vest4		0.32
MutPred		0.45		.;Gain of ubiquitination at R687 (P = 0.03);Gain of ubiquitination at R687 (P = 0.03);Gain of ubiquitination at R687 (P = 0.03);
MVP		0.39
MPC		1.5
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.29
gMVP		0.81

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: chr2-175309858;