NM_032634.4(PIGO):c.2007G>A (p.Trp669Ter) AND Hyperphosphatasia with intellectual disability syndrome 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 20, 2017
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:: RCV000705922.4

Allele description [Variation Report for NM_032634.4(PIGO):c.2007G>A (p.Trp669Ter)]

NM_032634.4(PIGO):c.2007G>A (p.Trp669Ter)

Gene:

PIGO:phosphatidylinositol glycan anchor biosynthesis class O [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_032634.4(PIGO):c.2007G>A (p.Trp669Ter)

HGVS:

NC_000009.12:g.35091880C>T
NG_031990.1:g.9722G>A
NM_001201484.2:c.1345-589G>A
NM_032634.4:c.2007G>AMANE SELECT
NM_152850.4:c.1345-589G>A
NP_116023.2:p.Trp669Ter
NC_000009.11:g.35091877C>T
NM_032634.3:c.2007G>A

Protein change:

W669*

Links:

dbSNP: rs1563996824

NCBI 1000 Genomes Browser:

rs1563996824

Molecular consequence:

NM_001201484.2:c.1345-589G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_152850.4:c.1345-589G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_032634.4:c.2007G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hyperphosphatasia with intellectual disability syndrome 2 (HPMRS2)
Synonyms:: GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 6; HYPERPHOSPHATASIA WITH IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME 2
Identifiers:: MONDO: MONDO:0013882; MedGen: C3553637; Orphanet: 247262; OMIM: 614749

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000834943	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 20, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22683086, 24417746, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000834943

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 20, 2017)

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

Mutations in PIGO, a member of the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation.

Krawitz PM, Murakami Y, Hecht J, Krüger U, Holder SE, Mortier GR, Delle Chiaie B, De Baere E, Thompson MD, Roscioli T, Kielbasa S, Kinoshita T, Mundlos S, Robinson PN, Horn D.

Am J Hum Genet. 2012 Jul 13;91(1):146-51. doi: 10.1016/j.ajhg.2012.05.004. Epub 2012 Jun 7.

PubMed [citation]

PMID:: 22683086
PMCID:: PMC3397269

PIGO mutations in intractable epilepsy and severe developmental delay with mild elevation of alkaline phosphatase levels.

Nakamura K, Osaka H, Murakami Y, Anzai R, Nishiyama K, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Kinoshita T, Matsumoto N, Saitsu H.

Epilepsia. 2014 Feb;55(2):e13-7. doi: 10.1111/epi.12508. Epub 2014 Jan 13.

PubMed [citation]

PMID:: 24417746

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000834943.4

#	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. Loss-of-function variants in PIGO are known to be pathogenic (PMID: 22683086, 24417746). This variant has not been reported in the literature in individuals with PIGO-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp669*) in the PIGO gene. It is expected to 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 20, 2024

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