NM_001346754.2(PIGW):c.281T>A (p.Leu94Ter) AND Hyperphosphatasia with intellectual disability syndrome 5

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 19, 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:: RCV001857868.4

Allele description [Variation Report for NM_001346754.2(PIGW):c.281T>A (p.Leu94Ter)]

NM_001346754.2(PIGW):c.281T>A (p.Leu94Ter)

Genes:

MYO19:myosin XIX [Gene - OMIM - HGNC]
PIGW:phosphatidylinositol glycan anchor biosynthesis class W [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_001346754.2(PIGW):c.281T>A (p.Leu94Ter)

HGVS:

NC_000017.11:g.36537382T>A
NG_052004.1:g.7621T>A
NM_001346754.2:c.281T>AMANE SELECT
NM_001346755.2:c.281T>A
NM_178517.3:c.281T>A
NM_178517.5:c.281T>A
NP_001333683.1:p.Leu94Ter
NP_001333684.1:p.Leu94Ter
NP_848612.2:p.Leu94Ter
NC_000017.10:g.34893231T>A

Protein change:

L94*

Links:

dbSNP: rs770634248

NCBI 1000 Genomes Browser:

rs770634248

Molecular consequence:

NM_001346754.2:c.281T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001346755.2:c.281T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_178517.5:c.281T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hyperphosphatasia with intellectual disability syndrome 5 (GPIBD11)
Synonyms:: GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 11
Identifiers:: MONDO: MONDO:0014457; MedGen: C4014958; Orphanet: 247262; OMIM: 616025

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002215324	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 19, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004228792	GenomeConnect - Invitae Patient Insights Network	no classification provided	not provided	unknown	phenotyping only

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002215324

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 19, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004228792

GenomeConnect - Invitae Patient Insights Network

no classification provided

not provided

unknown

phenotyping only

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
not provided	unknown	unknown	1	not provided	not provided	1	not provided	phenotyping only

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002215324.3

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

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 445649). This variant has not been reported in the literature in individuals affected with PIGW-related conditions. This variant is present in population databases (rs770634248, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Leu94*) in the PIGW gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 411 amino acid(s) of the PIGW protein.

#	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

From GenomeConnect - Invitae Patient Insights Network, SCV004228792.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	phenotyping only	not provided

Description

Variant interpreted as Uncertain significance and reported on 01-31-2021 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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

Last Updated: Feb 14, 2024

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