NM_002435.3(MPI):c.84_88del (p.Arg29fs) AND MPI-congenital disorder of glycosylation

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Feb 5, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001245427.8

Allele description [Variation Report for NM_002435.3(MPI):c.84_88del (p.Arg29fs)]

NM_002435.3(MPI):c.84_88del (p.Arg29fs)

Gene:

MPI:mannose phosphate isomerase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_002435.3(MPI):c.84_88del (p.Arg29fs)

HGVS:

NC_000015.10:g.74890594_74890598del
NG_008921.1:g.5526_5530del
NM_001289155.2:c.84_88del
NM_001289156.2:c.-7+505_-7+509del
NM_001289157.2:c.84_88del
NM_001330372.2:c.24_28del
NM_002435.3:c.84_88delMANE SELECT
NP_001276084.1:p.Arg29fs
NP_001276086.1:p.Arg29fs
NP_001317301.1:p.Arg9fs
NP_002426.1:p.Arg29fs
NC_000015.9:g.75182932_75182936del
NC_000015.9:g.75182935_75182939del
NM_002435.2:c.84_88del

Protein change:

R29fs

Links:

dbSNP: rs753839890

NCBI 1000 Genomes Browser:

rs753839890

Molecular consequence:

NM_001289155.2:c.84_88del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289157.2:c.84_88del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330372.2:c.24_28del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002435.3:c.84_88del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289156.2:c.-7+505_-7+509del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: MPI-congenital disorder of glycosylation
Synonyms:: CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib; CDG Ib; Congenital disorder of glycosylation type 1B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011257; MedGen: C1865145; Orphanet: 79319; OMIM: 602579

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001418715	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 9, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19862844, 28492532
SCV004193723	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 5, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001418715

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 9, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004193723

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 5, 2024)

unknown

clinical testing

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

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides.

Haeuptle MA, Hennet T.

Hum Mutat. 2009 Dec;30(12):1628-41. doi: 10.1002/humu.21126. Review.

PubMed [citation]

PMID:: 19862844

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001418715.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Arg29Valfs*5) in the MPI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPI are known to be pathogenic (PMID: 19862844). This variant is present in population databases (rs753839890, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MPI-related conditions. ClinVar contains an entry for this variant (Variation ID: 969962). For these reasons, this variant has been classified as Pathogenic.

#	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 Baylor Genetics, SCV004193723.2

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

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

Last Updated: Sep 29, 2024

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