NM_001034853.2(RPGR):c.3017_3018del (p.Glu1006fs) AND Primary ciliary dyskinesia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 4, 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:: RCV002966655.4

Allele description [Variation Report for NM_001034853.2(RPGR):c.3017_3018del (p.Glu1006fs)]

NM_001034853.2(RPGR):c.3017_3018del (p.Glu1006fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_001034853.2(RPGR):c.3017_3018del (p.Glu1006fs)

HGVS:

NC_000023.11:g.38285982TC[1]
NG_009553.1:g.46552AG[1]
NM_000328.3:c.1905+1112_1905+1113del
NM_001034853.2:c.3017_3018delMANE SELECT
NM_001367245.1:c.1902+1112_1902+1113del
NM_001367246.1:c.1719+1112_1719+1113del
NM_001367247.1:c.1572+4977_1572+4978del
NM_001367248.1:c.1602+4977_1602+4978del
NM_001367249.1:c.1569+4977_1569+4978del
NM_001367250.1:c.1569+4977_1569+4978del
NM_001367251.1:c.1386+4977_1386+4978del
NP_001030025.1:p.Glu1006fs
NC_000023.10:g.38145234_38145235del
NC_000023.10:g.38145235TC[1]

Protein change:

E1006fs

Molecular consequence:

NM_001034853.2:c.3017_3018del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000328.3:c.1905+1112_1905+1113del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367245.1:c.1902+1112_1902+1113del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367246.1:c.1719+1112_1719+1113del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367247.1:c.1572+4977_1572+4978del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367248.1:c.1602+4977_1602+4978del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367249.1:c.1569+4977_1569+4978del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367250.1:c.1569+4977_1569+4978del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367251.1:c.1386+4977_1386+4978del - 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
SCV003284270	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 4, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22264887, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003284270

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 4, 2022)

germline

clinical testing

PubMed (2)
[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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003284270.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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; 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. This variant has not been reported in the literature in individuals affected with RPGR (ORF15)-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1006Glyfs*72) in the RPGR (ORF15) gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 147 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: Sep 29, 2024

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