NM_017570.5(OPLAH):c.2362dup (p.His788fs) AND 5-Oxoprolinase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 25, 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:: RCV003643101.2

Allele description [Variation Report for NM_017570.5(OPLAH):c.2362dup (p.His788fs)]

NM_017570.5(OPLAH):c.2362dup (p.His788fs)

Gene:

OPLAH:5-oxoprolinase, ATP-hydrolysing [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_017570.5(OPLAH):c.2362dup (p.His788fs)

HGVS:

NC_000008.11:g.144055081dup
NG_032671.1:g.10606dup
NM_017570.5:c.2362dupMANE SELECT
NP_060040.1:p.His788fs
NC_000008.10:g.145109978_145109979insG
NC_000008.10:g.145109984dup

Protein change:

H788fs

Molecular consequence:

NM_017570.5:c.2362dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: 5-Oxoprolinase deficiency (OPLAHD)
Synonyms:: Oxoprolinuria due to 5-oxoprolinase deficiency; 5-alpha-oxoprolinase deficiency; 5-OXOPROLINURIA DUE TO 5-OXOPROLINASE DEFICIENCY
Identifiers:: MONDO: MONDO:0009825; MedGen: C0268525; Orphanet: 33572; OMIM: 260005; Human Phenotype Ontology: HP:0040142

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004371736	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 25, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21651516, 27477828, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004371736

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 25, 2023)

germline

clinical testing

PubMed (3)
[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

5-Oxoprolinase deficiency: report of the first human OPLAH mutation.

Almaghlouth IA, Mohamed JY, Al-Amoudi M, Al-Ahaidib L, Al-Odaib A, Alkuraya FS.

Clin Genet. 2012 Aug;82(2):193-6. doi: 10.1111/j.1399-0004.2011.01728.x. Epub 2011 Jun 30.

PubMed [citation]

PMID:: 21651516

Unravelling 5-oxoprolinuria (pyroglutamic aciduria) due to bi-allelic OPLAH mutations: 20 new mutations in 14 families.

Sass JO, Gemperle-Britschgi C, Tarailo-Graovac M, Patel N, Walter M, Jordanova A, Alfadhel M, Barić I, Çoker M, Damli-Huber A, Faqeih EA, García Segarra N, Geraghty MT, Jåtun BM, Kalkan Uçar S, Kriewitz M, Rauchenzauner M, Bilić K, Tournev I, Till C, Sayson B, Beumer D, et al.

Mol Genet Metab. 2016 Sep;119(1-2):44-9. doi: 10.1016/j.ymgme.2016.07.008. Epub 2016 Jul 22.

PubMed [citation]

PMID:: 27477828

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004371736.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with OPLAH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His788Profs*174) in the OPLAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OPLAH are known to be pathogenic (PMID: 21651516, 27477828).

#	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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