2-174445145-T-G

Variant names:

• chr2-174445145-T-G
• rs149791163
• NM_152529.7:c.2045A>C

Variant summary

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

The NM_152529.7(GPR155):​c.2045A>C​(p.Asn682Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,260 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N682S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPR155 NM_152529.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152529.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR155	NM_152529.7	MANE Select	c.2045A>C	p.Asn682Thr	missense	Exon 13 of 16	NP_689742.4
	GPR155	NM_001033045.4		c.2045A>C	p.Asn682Thr	missense	Exon 14 of 17	NP_001028217.1	Q7Z3F1
	GPR155	NM_001267050.2		c.2045A>C	p.Asn682Thr	missense	Exon 14 of 17	NP_001253979.1	Q7Z3F1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR155	ENST00000392552.7	TSL:1 MANE Select	c.2045A>C	p.Asn682Thr	missense	Exon 13 of 16	ENSP00000376335.2	Q7Z3F1
	GPR155	ENST00000295500.8	TSL:1	c.2045A>C	p.Asn682Thr	missense	Exon 14 of 17	ENSP00000295500.4	Q7Z3F1
	GPR155	ENST00000392551.6	TSL:1	c.2045A>C	p.Asn682Thr	missense	Exon 14 of 17	ENSP00000376334.2	Q7Z3F1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440260 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 717904

African (AFR) AF: 0.00 AC: 0 AN: 33004

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 85832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092508

Other (OTH) AF: 0.00 AC: 0 AN: 59628

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	0.074	T
Polyphen		0.86	P
Vest4		0.60
MutPred		0.41		Gain of glycosylation at N682 (P = 0.0554)
MVP		0.35
MPC		2.2
ClinPred		0.87	D
GERP RS		3.1
Varity_R		0.25
gMVP		0.63
Mutation Taster		=40/60	disease causing

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: rs149791163; hg19: chr2-175309873;