NM_000276.4(OCRL):c.577_578del (p.Glu193fs) AND Lowe syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 27, 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:: RCV003224765.1

Allele description

NM_000276.4(OCRL):c.577_578del (p.Glu193fs)

Gene:

OCRL:OCRL inositol polyphosphate-5-phosphatase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq26.1

Genomic location:

Preferred name:

NM_000276.4(OCRL):c.577_578del (p.Glu193fs)

HGVS:

NC_000023.11:g.129558856_129558857del
NG_008638.1:g.23582_23583del
NM_000276.4:c.577_578delMANE SELECT
NM_001318784.2:c.580_581del
NM_001587.4:c.577_578del
NP_000267.2:p.Glu193fs
NP_001305713.1:p.Glu194fs
NP_001578.2:p.Glu193fs
NC_000023.10:g.128692833_128692834del

Protein change:

E193fs

Molecular consequence:

NM_000276.4:c.577_578del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318784.2:c.580_581del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001587.4:c.577_578del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Lowe syndrome (OCRL)
Synonyms:: LOWE OCULOCEREBRORENAL SYNDROME; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 5-PHOSPHATASE DEFICIENCY; Oculocerebrorenal Syndrome
Identifiers:: MONDO: MONDO:0010645; MedGen: C0028860; Orphanet: 534; OMIM: 309000

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003919745	Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 27, 2023)	unknown	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

SCV003919745

Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 27, 2023)

unknown

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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

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 Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen, SCV003919745.1

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

Description

The proven change does not occur in the general population (gnomAD) (as of April 17, 2023). It has not yet been described in the literature. The variant represents a shift in the reading frame with a subsequent stop codon. This usually leads either to premature termination of translation or a so-called "nonsense-mediated mRNA decay". In both cases, there is a loss of function of the protein. Intolerance to haploinsufficiency has been described as a pathomechanism for the gene examined. Therefore, a pathogenetic relevance can be assumed with high probability. The variant is currently to be regarded as a "likely pathogenic variant" (ACMG criteria).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jan 13, 2025

ClinVar

Relating variation to medicine