NM_001034853.2(RPGR):c.2625dup (p.Gly876fs) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 8, 2021
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:: RCV002573575.4

Allele description [Variation Report for NM_001034853.2(RPGR):c.2625dup (p.Gly876fs)]

NM_001034853.2(RPGR):c.2625dup (p.Gly876fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_001034853.2(RPGR):c.2625dup (p.Gly876fs)

Other names:

NM_001034853.2:c.2625dup

HGVS:

NC_000023.11:g.38286375dup
NG_009553.1:g.46162dup
NM_000328.3:c.1905+720dup
NM_001034853.2:c.2625dupMANE SELECT
NM_001367245.1:c.1902+720dup
NM_001367246.1:c.1719+720dup
NM_001367247.1:c.1572+4585dup
NM_001367248.1:c.1602+4585dup
NM_001367249.1:c.1569+4585dup
NM_001367250.1:c.1569+4585dup
NM_001367251.1:c.1386+4585dup
NP_001030025.1:p.Gly876fs
NC_000023.10:g.38145626_38145627insT
NC_000023.10:g.38145628dup
NM_001034853.1:c.2625dup

Protein change:

G876fs

Molecular consequence:

NM_001034853.2:c.2625dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000328.3:c.1905+720dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001367245.1:c.1902+720dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001367246.1:c.1719+720dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001367247.1:c.1572+4585dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001367248.1:c.1602+4585dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001367249.1:c.1569+4585dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001367250.1:c.1569+4585dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001367251.1:c.1386+4585dup - 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
SCV003444599	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10932196, 28322733, 22264887, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003444599

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 8, 2021)

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

Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa.

Vervoort R, Lennon A, Bird AC, Tulloch B, Axton R, Miano MG, Meindl A, Meitinger T, Ciccodicola A, Wright AF.

Nat Genet. 2000 Aug;25(4):462-6.

PubMed [citation]

PMID:: 10932196

Quantitative Analysis of Retinal Structure Using Spectral-Domain Optical Coherence Tomography in RPGR-Associated Retinopathy.

Tee JJL, Carroll J, Webster AR, Michaelides M.

Am J Ophthalmol. 2017 Jun;178:18-26. doi: 10.1016/j.ajo.2017.03.012. Epub 2017 Mar 18.

PubMed [citation]

PMID:: 28322733
PMCID:: PMC5451208

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003444599.2

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

Description

This sequence change creates a premature translational stop signal (p.Gly876Argfs*203) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 277 amino acid(s) of the RPGR (ORF15) protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with retinitis pigmentosa (PMID: 10932196, 28322733). This variant is also known as g.ORF15+872_873insA and g.ORF15+872dup. 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. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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