NM_000276.4(OCRL):c.940-11G>A AND Lowe syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 11, 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:: RCV001855052.5

Allele description [Variation Report for NM_000276.4(OCRL):c.940-11G>A]

NM_000276.4(OCRL):c.940-11G>A

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

Xq26.1

Genomic location:

Preferred name:

NM_000276.4(OCRL):c.940-11G>A

HGVS:

NC_000023.11:g.129562373G>A
NG_008638.1:g.27099G>A
NM_000276.4:c.940-11G>AMANE SELECT
NM_001318784.2:c.943-11G>A
NM_001587.4:c.940-11G>A
NC_000023.10:g.128696350G>A
NM_000276.3:c.940-11G>A

Links:

dbSNP: rs776743373

NCBI 1000 Genomes Browser:

rs776743373

Molecular consequence:

NM_000276.4:c.940-11G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001318784.2:c.943-11G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001587.4:c.940-11G>A - intron variant - [Sequence Ontology: SO:0001627]

Functional consequence:

Variation affecting splicing function of RNA [Variation Ontology: 0397]

Condition(s)

Name:: Lowe syndrome (OCRL)
Synonyms:: Oculocerebrorenal Syndrome; Lowe oculocerebrorenal syndrome; Phosphatidylinositol 4,5-bisphosphate 5-phosphatase deficiency
Identifiers:: MONDO: MONDO:0010645; MedGen: C0028860; Orphanet: 534; OMIM: 309000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002240528	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 11, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16381338, 25480730, 28803024, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002240528

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 11, 2022)

germline

clinical testing

PubMed (4)
[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

Identification of OCRL1 mutations in two Taiwanese Lowe syndrome patients.

Chou YY, Chao SC, Chiou YY, Lin SJ.

Acta Paediatr Taiwan. 2005 Jul-Aug;46(4):226-9.

PubMed [citation]

PMID:: 16381338

Characterization of 28 novel patients expands the mutational and phenotypic spectrum of Lowe syndrome.

Recker F, Zaniew M, Böckenhauer D, Miglietti N, Bökenkamp A, Moczulska A, Rogowska-Kalisz A, Laube G, Said-Conti V, Kasap-Demir B, Niemirska A, Litwin M, Siteń G, Chrzanowska KH, Krajewska-Walasek M, Sethi SK, Tasic V, Anglani F, Addis M, Wasilewska A, Szczepańska M, Pawlaczyk K, et al.

Pediatr Nephrol. 2015 Jun;30(6):931-43. doi: 10.1007/s00467-014-3013-2. Epub 2014 Dec 6.

PubMed [citation]

PMID:: 25480730

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002240528.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in retention of 9 nucleotides in intron 10 and introduces a premature termination codon (PMID: 16381338, 28803024). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 279859). This variant has been observed in individuals with Lowe syndrome (PMID: 16381338, 25480730, 28803024). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the OCRL gene. It does not directly change the encoded amino acid sequence of the OCRL protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.

#	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: Feb 14, 2024

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