9-36147855-C-T

Variant names:

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

Variant summary

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

The NM_022343.4(GLIPR2):​c.83C>T​(p.Pro28Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,440,802 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. P28Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GLIPR2 NM_022343.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

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>T	p.Pro28Leu	missense	Exon 2 of 5	NP_071738.1	Q9H4G4
	GLIPR2	NM_001287013.2		c.128C>T	p.Pro43Leu	missense	Exon 2 of 5	NP_001273942.1
	GLIPR2	NM_001287010.2		c.83C>T	p.Pro28Leu	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>T	p.Pro28Leu	missense	Exon 2 of 5	ENSP00000367196.4	Q9H4G4
	GLIPR2	ENST00000377959.5	TSL:3	c.83C>T	p.Pro28Leu	missense	Exon 2 of 4	ENSP00000367195.1	Q5VZR0
	GLIPR2	ENST00000396613.7	TSL:4	c.83C>T	p.Pro28Leu	missense	Exon 2 of 3	ENSP00000379857.4	A0A088AWP7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440802 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 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: 0.0000253 AC: 1 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1092884

Other (OTH) AF: 0.00 AC: 0 AN: 59704

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		5.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Benign	0.22
Sift	Benign	0.068	T
Sift4G	Uncertain	0.0030	D
Polyphen		0.12	B
Vest4		0.76
MutPred		0.66		Loss of catalytic residue at P27 (P = 0.0191)
MVP		0.60
MPC		0.55
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.77
gMVP		0.72
Mutation Taster		=76/24	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;