NM_001034853.2(RPGR):c.2543del (p.Glu848fs) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 31, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003537467.2

Allele description [Variation Report for NM_001034853.2(RPGR):c.2543del (p.Glu848fs)]

NM_001034853.2(RPGR):c.2543del (p.Glu848fs)

Gene:

RPGR:retinitis pigmentosa GTPase regulator [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_001034853.2(RPGR):c.2543del (p.Glu848fs)

HGVS:

NC_000023.11:g.38286456del
NG_009553.1:g.46080del
NM_000328.3:c.1905+638del
NM_001034853.2:c.2543delMANE SELECT
NM_001367245.1:c.1902+638del
NM_001367246.1:c.1719+638del
NM_001367247.1:c.1572+4503del
NM_001367248.1:c.1602+4503del
NM_001367249.1:c.1569+4503del
NM_001367250.1:c.1569+4503del
NM_001367251.1:c.1386+4503del
NP_001030025.1:p.Glu848fs
NC_000023.10:g.38145709del
NC_000023.10:g.38145709del
NM_001034853.1:c.2543del

Protein change:

E848fs

Links:

dbSNP: rs1233849070

NCBI 1000 Genomes Browser:

rs1233849070

Molecular consequence:

NM_001034853.2:c.2543del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000328.3:c.1905+638del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367245.1:c.1902+638del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367246.1:c.1719+638del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367247.1:c.1572+4503del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367248.1:c.1602+4503del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367249.1:c.1569+4503del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367250.1:c.1569+4503del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367251.1:c.1386+4503del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Primary ciliary dyskinesia
Synonyms:: Ciliary dyskinesia
Identifiers:: MONDO: MONDO:0016575; MedGen: C0008780; OMIM: PS244400; Human Phenotype Ontology: HP:0012265

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004299789	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 31, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22264887, 12402343, 25352739, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004299789

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 31, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy.

Thiadens AA, Phan TM, Zekveld-Vroon RC, Leroy BP, van den Born LI, Hoyng CB, Klaver CC; Writing Committee for the Cone Disorders Study Group Consortium, Roosing S, Pott JW, van Schooneveld MJ, van Moll-Ramirez N, van Genderen MM, Boon CJ, den Hollander AI, Bergen AA, De Baere E, Cremers FP, Lotery AJ.

Ophthalmology. 2012 Apr;119(4):819-26. doi: 10.1016/j.ophtha.2011.10.011. Epub 2012 Jan 20.

PubMed [citation]

PMID:: 22264887

Ten novel ORF15 mutations confirm mutational hot spot in the RPGR gene in European patients with X-linked retinitis pigmentosa.

Pusch CM, Broghammer M, Jurklies B, Besch D, Jacobi FK.

Hum Mutat. 2002 Nov;20(5):405.

PubMed [citation]

PMID:: 12402343

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004299789.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the RPGR (ORF15) protein in which other variant(s) (p.Leu1130Lysfs*13 ) have been determined to be pathogenic (PMID: 22264887). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 866274). This variant is also known as g.ORF15+414delA . This premature translational stop signal has been observed in individuals with X-linked retinitis pigmentosa (PMID: 12402343, 25352739). It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Glu848Glyfs*241) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 305 amino acid(s) of the RPGR (ORF15) protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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