VCV000143151.43 - ClinVar

NM_016247.4(IMPG2):c.3262C>T (p.Arg1088Ter)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(12)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_016247.4(IMPG2):c.3262C>T (p.Arg1088Ter)

Variation ID: 143151 Accession: VCV000143151.43

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q12.3 3: 101231117 (GRCh38) [ NCBI UCSC ] 3: 100949961 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Aug 10, 2014	Oct 20, 2024	Jan 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_016247.4:c.3262C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_057331.2:p.Arg1088Ter	nonsense
NC_000003.12:g.101231117G>A
NC_000003.11:g.100949961G>A
NG_028284.1:g.94459C>T

Protein change

R1088*

Other names

Canonical SPDI

NC_000003.12:101231116:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00003

The Genome Aggregation Database (gnomAD), exomes 0.00004

Exome Aggregation Consortium (ExAC) 0.00006

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA270121 dbSNP: rs199867882 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
IMPG2		-	-	GRCh38 GRCh37	963	979

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Retinitis pigmentosa	Pathogenic (1)	no assertion criteria provided	-	RCV000132676.3
not provided	Pathogenic/Likely pathogenic (6)	criteria provided, multiple submitters, no conflicts	Jan 22, 2024	RCV000585301.34
Autosomal recessive retinitis pigmentosa	Pathogenic (1)	no assertion criteria provided	Jul 2, 2019	RCV001257827.3
Retinal dystrophy	Pathogenic (1)	criteria provided, single submitter	Nov 23, 2018	RCV001074065.4
Vitelliform macular dystrophy 5	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Jul 11, 2023	RCV001270127.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 11, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Macular dystrophy, vitelliform, 5 Affected status: unknown Allele origin: germline	Knight Diagnostic Laboratories, Oregon Health and Sciences University Accession: SCV001448996.1 First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020	Number of individuals with the variant: 1 Clinical Features: Functional abnormality of the bladder (present) , Bloody diarrhea (present) , Aganglionic megacolon (present) , Chest pain (present) , Abnormal peripheral nervous system morphology (present) … (more) Functional abnormality of the bladder (present) , Bloody diarrhea (present) , Aganglionic megacolon (present) , Chest pain (present) , Abnormal peripheral nervous system morphology (present) , Peripheral neuropathy (present) , Hand tremor (present) , EMG abnormality (present) , Abnormality of muscle physiology (present) , Abnormality of peripheral nerve conduction (present) , Stuttering (present) , Anxiety (present) , Behavioral abnormality (present) , Depressivity (present) , Tinnitus (present) , Pes cavus (present) , Abnormality of the foot (present) , Hammertoe (present) , Peripheral axonal neuropathy (present) , Skeletal muscle atrophy (present) , Generalized hypotonia (present) , Hemiparesis (present) , Back pain (present) , Chronic pain (present) , Hernia (present) , Abnormality of the male genitalia (present) , Urinary urgency (present) , Abnormality of the nervous system (present) , Movement disorder (present) , Muscle weakness (present) , Abnormality of peripheral nerves (present) , Foot pain (present) , Knee pain (present) , Pain (present) , Acroparesthesia (present) , Clumsiness (present) , Incoordination (present) , Abdominal pain (present) , Nausea (present) , Allergic rhinitis (present) , Headache (present) , Brisk reflexes (present) , Weight loss (present) , Blotching pigmentation of the skin (present) , Gait disturbance (present) , Postural instability (present) , Gait imbalance (present) , Epididymitis (present) , Orchitis (present) , Dysuria (present) , Scrotal pain (present) (less) Sex: male
Pathogenic (Nov 05, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001773846.1 First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021	Comment: Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more) Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20673862, 31264916, 24876279, 25525159) (less)
Likely pathogenic (Mar 07, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Vitelliform macular dystrophy 5 Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002581313.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PVS1, PM2_SUP	Number of individuals with the variant: 1 Sex: male
Pathogenic (Jul 11, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Vitelliform macular dystrophy 5 (Autosomal dominant inheritance) Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV004027647.1 First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023	Comment: Criteria applied: PVS1,PS4,PM2_SUP Clinical Features: Macular dystrophy (present) , Vitelliform-like macular lesions (present) Sex: female
Likely pathogenic (Jul 01, 2017)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV000693113.30 First in ClinVar: Mar 03, 2018 Last updated: Oct 20, 2024	Number of individuals with the variant: 1
Pathogenic (Nov 23, 2018)	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme) Method: clinical testing	Retinal dystrophy Affected status: yes Allele origin: germline	Blueprint Genetics Accession: SCV001239634.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 Comment: My Retina Tracker patient
Pathogenic (Jan 22, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001411339.5 First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024	Publications: PubMed (1) PubMed: 20673862 Comment: This sequence change creates a premature translational stop signal (p.Arg1088) in the IMPG2 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Arg1088) in the IMPG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IMPG2 are known to be pathogenic (PMID: 20673862). This variant is present in population databases (rs199867882, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 20673862). ClinVar contains an entry for this variant (Variation ID: 143151). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
pathogenic (-)	no assertion criteria provided Method: not provided	Retinitis pigmentosa Affected status: not provided Allele origin: not provided	Department of Ophthalmology and Visual Sciences Kyoto University Accession: SCV000172628.1 First in ClinVar: Aug 10, 2014 Last updated: Aug 10, 2014	Comment: Converted during submission to Pathogenic.
Pathogenic (Jul 02, 2019)	no assertion criteria provided Method: literature only	Autosomal recessive Retinitis Pigmentosa Affected status: yes Allele origin: germline	Faculty of Health Sciences, Beirut Arab University Accession: SCV001434690.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020	Publications: PubMed (1) PubMed: 31264916 Number of individuals with the variant: 1 Ethnicity/Population group: Arab
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001918343.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001956709.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001973638.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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Comment:

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20673862, 31264916, 24876279, 25525159)

Comment:

This sequence change creates a premature translational stop signal (p.Arg1088*) in the IMPG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IMPG2 are known to be pathogenic (PMID: 20673862). This variant is present in population databases (rs199867882, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 20673862). ClinVar contains an entry for this variant (Variation ID: 143151). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Homozygous and heterozygous retinal phenotypes in families harbouring IMPG2 mutations.	Khan AO	Ophthalmic genetics	2019	PMID: 31264916
Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa.	Bandah-Rozenfeld D	American journal of human genetics	2010	PMID: 20673862

Text-mined citations for rs199867882 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_016247.4(IMPG2):c.3262C>T (p.Arg1088Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs199867882 ...