NM_022343.4:c.269A>C

Variant names:

• chr9-36150914-A-C
• NM_022343.4:c.269A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022343.4(GLIPR2):​c.269A>C​(p.Tyr90Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLIPR2 NM_022343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.50
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

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.269A>C	p.Tyr90Ser	missense	Exon 4 of 5	NP_071738.1	Q9H4G4
	GLIPR2	NM_001287013.2		c.314A>C	p.Tyr105Ser	missense	Exon 4 of 5	NP_001273942.1
	GLIPR2	NM_001287011.2		c.269A>C	p.Tyr90Ser	missense	Exon 4 of 5	NP_001273940.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIPR2	ENST00000377960.9	TSL:1 MANE Select	c.269A>C	p.Tyr90Ser	missense	Exon 4 of 5	ENSP00000367196.4	Q9H4G4
	GLIPR2	ENST00000885959.1		c.56A>C	p.Tyr19Ser	missense	Exon 2 of 3	ENSP00000556018.1
	GLIPR2	ENST00000377959.5	TSL:3	c.226+2264A>C		intron	N/A	ENSP00000367195.1	Q5VZR0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	4.4	H
PhyloP100		6.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.95	P
Vest4		0.86
MutPred		0.77		Gain of disorder (P = 0.01)
MVP		0.56
MPC		1.3
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.97
gMVP		0.94
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr9-36150911;