VCV001707409.2 - ClinVar

NM_001034853.2(RPGR):c.1302dup (p.Leu435fs)

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.

(5)

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.

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_001034853.2(RPGR):c.1302dup (p.Leu435fs)

Variation ID: 1707409 Accession: VCV001707409.2

Type and length

Duplication, 1 bp

Location

Cytogenetic: Xp11.4 X: 38297395-38297396 (GRCh38) [ NCBI UCSC ] X: 38156648-38156649 (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	Oct 1, 2022	Mar 11, 2023	Jun 22, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001034853.2:c.1302dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001030025.1:p.Leu435fs	frameshift
NM_000328.3:c.1302dup	NP_000319.1:p.Leu435fs	frameshift
NM_001367245.1:c.1299dup	NP_001354174.1:p.Leu434fs	frameshift
NM_001367246.1:c.1116dup	NP_001354175.1:p.Leu373fs	frameshift
NM_001367247.1:c.1302dup	NP_001354176.1:p.Leu435fs	frameshift
NM_001367248.1:c.1332dup	NP_001354177.1:p.Leu445fs	frameshift
NM_001367249.1:c.1299dup	NP_001354178.1:p.Leu434fs	frameshift
NM_001367250.1:c.1299dup	NP_001354179.1:p.Leu434fs	frameshift
NM_001367251.1:c.1116dup	NP_001354180.1:p.Leu373fs	frameshift
NR_159803.1:n.1504dup		non-coding transcript variant
NR_159804.1:n.1378dup		non-coding transcript variant
NR_159805.1:n.1444dup		non-coding transcript variant
NR_159806.1:n.1444dup		non-coding transcript variant
NR_159807.1:n.1444dup		non-coding transcript variant
NR_159808.1:n.1556dup		non-coding transcript variant
NC_000023.11:g.38297396dup
NC_000023.10:g.38156649dup
NG_009553.1:g.35140dup

... more HGVS ... less HGVS

Protein change

L373fs, L434fs, L435fs, L445fs

Other names

Canonical SPDI

NC_000023.11:38297395:A:AA

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.

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

Links

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.
RPGR		-	-	GRCh38 GRCh37	1512	1685

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, X-linked, and sinorespiratory infections, with or without deafness	Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jun 22, 2022	RCV002286325.2
X-linked cone-rod dystrophy 1	Likely pathogenic (1)	criteria provided, single submitter	May 10, 2022	RCV003147755.1
Retinitis pigmentosa 3	Likely pathogenic (1)	criteria provided, single submitter	May 10, 2022	RCV003147754.1
Macular degeneration, X-linked atrophic	Likely pathogenic (1)	criteria provided, single submitter	May 10, 2022	RCV003147756.1

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.
Likely pathogenic (Jun 22, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness (X-linked dominant inheritance) Affected status: yes Allele origin: unknown	Wangler Lab, Baylor College of Medicine Accession: SCV002574700.1 First in ClinVar: Oct 01, 2022 Last updated: Oct 01, 2022	Publications: PubMed (1) PubMed: 8673101 Comment: This single nucleotide duplication at c.1302 (p.L435Sfs18) in RPGR has not been observed in population databases (PM2).This frameshift variant is located in exon 11 of … (more) This single nucleotide duplication at c.1302 (p.L435Sfs18) in RPGR has not been observed in population databases (PM2).This frameshift variant is located in exon 11 of 19 and is predicted to be deleterious. The resulting frameshift is predicted to result in nonsense mediated decay which has been described as a mechanism of disease (PVS1)(PMID:8673101). This variant was seen on exome through the Texome Project (R01HG011795) and determine to be likely pathogenic. (less) Clinical Features: Rod-cone dystrophy (present) , Hearing impairment (present) , Macrocephaly (present) , Normal pressure hydrocephalus (present) , Nevus flammeus (present) , Vertigo (present) , Blindness (present) Sex: male Ethnicity/Population group: European Testing laboratory: Org:1006
Likely pathogenic (May 10, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV003835592.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023
Likely pathogenic (May 10, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Macular degeneration, X-linked atrophic Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV003835593.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023
Likely pathogenic (May 10, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Retinitis pigmentosa 3 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV003836219.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023
Likely pathogenic (May 10, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	X-linked cone-rod dystrophy 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV003835599.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023

Comment:

This single nucleotide duplication at c.1302 (p.L435Sfs*18) in RPGR has not been observed in population databases (PM2).This frameshift variant is located in exon 11 of 19 and is predicted to be deleterious. The resulting frameshift is predicted to result in nonsense mediated decay which has been described as a mechanism of disease (PVS1)(PMID:8673101). This variant was seen on exome through the Texome Project (R01HG011795) and determine to be likely 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
A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).	Meindl A	Nature genetics	1996	PMID: 8673101

Text-mined citations for this variant ...

Record last updated Aug 06, 2023

ClinVar Genomic variation as it relates to human health

NM_001034853.2(RPGR):c.1302dup (p.Leu435fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...