rs786205564

Positions:

• chr3-101244057-C-T

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The ENST00000193391.8(IMPG2):​c.2274G>A​(p.Trp758Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IMPG2 ENST00000193391.8 stop_gained
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:5
• Conservation: PhyloP100: 0.679

Genes affected

IMPG2 (HGNC:18362): (interphotoreceptor matrix proteoglycan 2) The protein encoded by this gene binds chondroitin sulfate and hyaluronan and is a proteoglycan. The encoded protein plays a role in the organization of the interphotoreceptor matrix and may promote the growth and maintenance of the light-sensitive photoreceptor outer segment. Defects in this gene are a cause of retinitis pigmentosa type 56 and maculopathy, IMPG2-related.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Pathogenic. Variant got 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-101244057-C-T is Pathogenic according to our data. Variant chr3-101244057-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-101244057-C-T is described in Lovd as [Likely_pathogenic]. Variant chr3-101244057-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPG2	NM_016247.4	c.2274G>A	p.Trp758Ter	stop_gained	13/19	ENST00000193391.8	NP_057331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPG2	ENST00000193391.8	c.2274G>A	p.Trp758Ter	stop_gained	13/19	1	NM_016247.4	ENSP00000193391	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:2

Likely pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Aug 10, 2021	- -
Likely pathogenic, flagged submission	research	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	-	- -

Autosomal recessive retinitis pigmentosa Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

Faculty of Health Sciences, Beirut Arab University

Sep 03, 2018

- -

Vitelliform macular dystrophy 5 Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 17, 2024

- -

Retinitis pigmentosa Pathogenic:1

Pathogenic, no assertion criteria provided

research

Sharon lab, Hadassah-Hebrew University Medical Center

Jun 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	32
DANN	Uncertain	0.98
Eigen	Uncertain	0.29
Eigen_PC	Benign	-0.036
FATHMM_MKL	Benign	0.030	N
MutationTaster	Benign	1.0	A
Vest4		0.10
GERP RS		2.9

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

Publications

LitVar

Other links and lift over

dbSNP: rs786205564; hg19: chr3-100962901; COSMIC: COSV51982029;