NM_001034853.2(RPGR):c.3221_3225del (p.Glu1074fs) AND RPGR-related retinopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 2, 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:: RCV003226116.3

Allele description [Variation Report for NM_001034853.2(RPGR):c.3221_3225del (p.Glu1074fs)]

NM_001034853.2(RPGR):c.3221_3225del (p.Glu1074fs)

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.3221_3225del (p.Glu1074fs)

Other names:

NM_001034853.2:c.3221_3225del

HGVS:

NC_000023.11:g.38285774_38285778del
NG_009553.1:g.46758_46762del
NM_000328.3:c.1905+1316_1905+1320del
NM_001034853.2:c.3221_3225delMANE SELECT
NM_001367245.1:c.1902+1316_1902+1320del
NM_001367246.1:c.1719+1316_1719+1320del
NM_001367247.1:c.1572+5181_1572+5185del
NM_001367248.1:c.1602+5181_1602+5185del
NM_001367249.1:c.1569+5181_1569+5185del
NM_001367250.1:c.1569+5181_1569+5185del
NM_001367251.1:c.1386+5181_1386+5185del
NP_001030025.1:p.Glu1074fs
NC_000023.10:g.38145027_38145031del

Protein change:

E1074fs

Molecular consequence:

NM_001034853.2:c.3221_3225del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_000328.3:c.1905+1316_1905+1320del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367245.1:c.1902+1316_1902+1320del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367246.1:c.1719+1316_1719+1320del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367247.1:c.1572+5181_1572+5185del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367248.1:c.1602+5181_1602+5185del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367249.1:c.1569+5181_1569+5185del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367250.1:c.1569+5181_1569+5185del - intron variant - [Sequence Ontology: SO:0001627]
NM_001367251.1:c.1386+5181_1386+5185del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: RPGR-related retinopathy
Synonyms:: RPGR retinopathy
Identifiers:: MONDO: MONDO:0100437; MedGen: CN305589

Recent activity

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SDHC [Charadrius vociferus]
SDHC [Charadrius vociferus]
Gene ID:104282689

Gene
LOC101746025 [Bombyx mori]
LOC101746025 [Bombyx mori]
Gene ID:101746025

Gene
Aacs acetoacetyl-CoA synthetase [Rattus norvegicus]
Aacs acetoacetyl-CoA synthetase [Rattus norvegicus]
Gene ID:65984

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003922285	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 2, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003922285

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 2, 2023)

germline

curation

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	curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003922285.1

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

Description

The hemizygous p.Glu1074GlyfsTer3 variant in RPGR was identified by our study in one individual with retinitis pigmentosa. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein‚Äôs amino acid sequence beginning at position 1074 and leads to a premature termination codon 3 amino acids downstream. This termination codon occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Loss of function of the RPGR gene is an established disease mechanism in X-linked retinitis pigmentosa 3. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1_Moderate, PM2_Supporting (Richards 2015).

#	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: Jun 23, 2024

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