NM_001034853.2(RPGR):c.3351G>C (p.Glu1117Asp) AND Primary ciliary dyskinesia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 22, 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:: RCV002664321.4

Allele description [Variation Report for NM_001034853.2(RPGR):c.3351G>C (p.Glu1117Asp)]

NM_001034853.2(RPGR):c.3351G>C (p.Glu1117Asp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_001034853.2(RPGR):c.3351G>C (p.Glu1117Asp)

HGVS:

NC_000023.11:g.38285648C>G
NG_009553.1:g.46888G>C
NM_000328.3:c.1905+1446G>C
NM_001034853.1:c.3351G>C
NM_001034853.2:c.3351G>CMANE SELECT
NM_001367245.1:c.1902+1446G>C
NM_001367246.1:c.1719+1446G>C
NM_001367247.1:c.1572+5311G>C
NM_001367248.1:c.1602+5311G>C
NM_001367249.1:c.1569+5311G>C
NM_001367250.1:c.1569+5311G>C
NM_001367251.1:c.1386+5311G>C
NP_001030025.1:p.Glu1117Asp
NC_000023.10:g.38144901C>G

Protein change:

E1117D

Molecular consequence:

NM_000328.3:c.1905+1446G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001367245.1:c.1902+1446G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001367246.1:c.1719+1446G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001367247.1:c.1572+5311G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001367248.1:c.1602+5311G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001367249.1:c.1569+5311G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001367250.1:c.1569+5311G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001367251.1:c.1386+5311G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001034853.2:c.3351G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003525456	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525456

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 22, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV003525456.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RPGR (ORF15) protein function. ClinVar contains an entry for this variant (Variation ID: 2203444). This variant has not been reported in the literature in individuals affected with RPGR (ORF15)-related conditions. 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 replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1117 of the RPGR (ORF15) protein (p.Glu1117Asp).

#	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: Nov 3, 2024

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Relating variation to medicine