9-36147855-C-G

Variant names:

• chr9-36147855-C-G
• rs771790962
• NM_022343.4:c.83C>G

Variant summary

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

The NM_022343.4(GLIPR2):​c.83C>G​(p.Pro28Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000276 in 1,593,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P28Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: GLIPR2 NM_022343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• Publications: 1 publications found

Genes affected

GLIPR2 (HGNC:18007): (GLI pathogenesis related 2) Enables protein homodimerization activity. Involved in positive regulation of ERK1 and ERK2 cascade; positive regulation of epithelial cell migration; and positive regulation of epithelial to mesenchymal transition. Located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022343.4. 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
	GLIPR2	NM_022343.4	MANE Select	c.83C>G	p.Pro28Arg	missense	Exon 2 of 5	NP_071738.1	Q9H4G4
	GLIPR2	NM_001287013.2		c.128C>G	p.Pro43Arg	missense	Exon 2 of 5	NP_001273942.1
	GLIPR2	NM_001287010.2		c.83C>G	p.Pro28Arg	missense	Exon 2 of 4	NP_001273939.1	Q5VZR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIPR2	ENST00000377960.9	TSL:1 MANE Select	c.83C>G	p.Pro28Arg	missense	Exon 2 of 5	ENSP00000367196.4	Q9H4G4
	GLIPR2	ENST00000377959.5	TSL:3	c.83C>G	p.Pro28Arg	missense	Exon 2 of 4	ENSP00000367195.1	Q5VZR0
	GLIPR2	ENST00000396613.7	TSL:4	c.83C>G	p.Pro28Arg	missense	Exon 2 of 3	ENSP00000379857.4	A0A088AWP7

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251464 AF XY: 0.0000441

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000761

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000285 AC: 41 AN: 1440802 Hom.: 0 Cov.: 26 AF XY: 0.0000306 AC XY: 22 AN XY: 718080

African (AFR) AF: 0.00 AC: 0 AN: 33034

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.000884 AC: 35 AN: 39586

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092884

Other (OTH) AF: 0.0000502 AC: 3 AN: 59704

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000576 AC: 7

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.22
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.77	P
Vest4		0.76
MutPred		0.68		Gain of MoRF binding (P = 0.0025)
MVP		0.69
MPC		0.65
ClinPred		0.86	D
GERP RS		5.5
Varity_R		0.76
gMVP		0.68
Mutation Taster		=70/30	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: rs771790962; hg19: chr9-36147852;