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NM_032634.4(PIGO):c.3069G>T (p.Gln1023His) AND Hyperphosphatasia with intellectual disability syndrome 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 29, 2021
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:
RCV001344466.7

Allele description [Variation Report for NM_032634.4(PIGO):c.3069G>T (p.Gln1023His)]

NM_032634.4(PIGO):c.3069G>T (p.Gln1023His)

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.3069G>T (p.Gln1023His)
HGVS:
  • NC_000009.12:g.35090066C>A
  • NG_031990.1:g.11536G>T
  • NM_001201484.2:c.1818G>T
  • NM_032634.4:c.3069G>TMANE SELECT
  • NM_152850.4:c.1818G>T
  • NP_001188413.1:p.Gln606His
  • NP_116023.2:p.Gln1023His
  • NP_690577.2:p.Gln606His
  • NC_000009.11:g.35090063C>A
Protein change:
Q1023H
Links:
dbSNP: rs746286276
NCBI 1000 Genomes Browser:
rs746286276
Molecular consequence:
  • NM_001201484.2:c.1818G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032634.4:c.3069G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_152850.4:c.1818G>T - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001538520Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Apr 29, 2021)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001538520.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PIGO-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 1023 of the PIGO protein (p.Gln1023His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant also falls at the last nucleotide of exon 9 of the PIGO coding sequence, which is part of the consensus splice site for this exon.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024