rs73648727

Variant names:

• chr9-36162429-C-T
• rs73648727
• NM_022343.4:c.372C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_022343.4(GLIPR2):​c.372C>T​(p.Asp124Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: GLIPR2 NM_022343.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.11
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 9-36162429-C-T is Benign according to our data. Variant chr9-36162429-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 727326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.11 with no splicing effect.

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.372C>T	p.Asp124Asp	synonymous	Exon 5 of 5	NP_071738.1	Q9H4G4
	GLIPR2	NM_001287013.2		c.417C>T	p.Asp139Asp	synonymous	Exon 5 of 5	NP_001273942.1
	GLIPR2	NM_001287010.2		c.294C>T	p.Asp98Asp	synonymous	Exon 4 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.372C>T	p.Asp124Asp	synonymous	Exon 5 of 5	ENSP00000367196.4	Q9H4G4
	GLIPR2	ENST00000377959.5	TSL:3	c.294C>T	p.Asp98Asp	synonymous	Exon 4 of 4	ENSP00000367195.1	Q5VZR0
	GLIPR2	ENST00000885959.1		c.159C>T	p.Asp53Asp	synonymous	Exon 3 of 3	ENSP00000556018.1

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 259 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00584

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000430 AC: 108 AN: 251292 AF XY: 0.000324

Gnomad AFR exome AF: 0.00542

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000196 AC: 286 AN: 1461660 Hom.: 0 Cov.: 31 AF XY: 0.000172 AC XY: 125 AN XY: 727134

African (AFR) AF: 0.00652 AC: 218 AN: 33454

American (AMR) AF: 0.000246 AC: 11 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111918

Other (OTH) AF: 0.000364 AC: 22 AN: 60386

GnomAD4 genome AF: 0.00170 AC: 259 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74468

African (AFR) AF: 0.00582 AC: 242 AN: 41564

American (AMR) AF: 0.000523 AC: 8 AN: 15298

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000788 Hom.: 0

Bravo AF: 0.00184

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.24
DANN	Benign	0.52
PhyloP100		-2.1

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: rs73648727; hg19: chr9-36162426; COSMIC: COSV65029082;