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NM_001034853.2(RPGR):c.2873_2874insGGATGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGA (p.Glu959fs) AND Primary ciliary dyskinesia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 14, 2022
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:
RCV002829620.2

Allele description

NM_001034853.2(RPGR):c.2873_2874insGGATGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGA (p.Glu959fs)

Gene:
RPGR:retinitis pigmentosa GTPase regulator [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
Xp11.4
Genomic location:
Preferred name:
NM_001034853.2(RPGR):c.2873_2874insGGATGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGA (p.Glu959fs)
HGVS:
  • NC_000023.11:g.38286197_38286198insATCCTCCCCCTCCCATTCTCCTTCCTCCTCTTCCCCCTCCCCTTCTCCATCCTCCCCTTCCCCTTCTCCTTCCTCC
  • NG_009553.1:g.46339_46410GGA[2]AGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGATGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGA[1]
  • NM_000328.3:c.1905+968_1905+969insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NM_001034853.2:c.2873_2874insGGATGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAMANE SELECT
  • NM_001367245.1:c.1902+968_1902+969insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NM_001367246.1:c.1719+968_1719+969insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NM_001367247.1:c.1572+4833_1572+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NM_001367248.1:c.1602+4833_1602+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NM_001367249.1:c.1569+4833_1569+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NM_001367250.1:c.1569+4833_1569+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NM_001367251.1:c.1386+4833_1386+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT
  • NP_001030025.1:p.Glu959fs
  • NC_000023.10:g.38145378_38145379insTCCCCCTCCCATTCTCCTTCCTCCTCTTCCCCCTCCCCTTCTCCATCCTCCCCTTCCCCTTCTCCTTCCTCCATCC
  • NC_000023.10:g.38145450_38145451insATCCTCCCCCTCCCATTCTCCTTCCTCCTCTTCCCCCTCCCCTTCTCCATCCTCCCCTTCCCCTTCTCCTTCCTCC
Protein change:
E959fs
Molecular consequence:
  • NM_001034853.2:c.2873_2874insGGATGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_000328.3:c.1905+968_1905+969insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367245.1:c.1902+968_1902+969insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367246.1:c.1719+968_1719+969insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367247.1:c.1572+4833_1572+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367248.1:c.1602+4833_1602+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367249.1:c.1569+4833_1569+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367250.1:c.1569+4833_1569+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001367251.1:c.1386+4833_1386+4834insGGAGGAAGGAGAAGGGGAAGGGGAGGATGGAGAAGGGGAGGGGGAAGAGGAGGAAGGAGAATGGGAGGGGGAGGAT - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003218571Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 14, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV003218571.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Glu959Aspfs*145) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 194 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 variant has not been reported in the literature in individuals affected with RPGR (ORF15)-related conditions. 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; Invitae). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 14, 2024