NM_002435.3(MPI):c.845-2del AND MPI-congenital disorder of glycosylation

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Feb 3, 2023
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:: RCV000668458.2

Allele description [Variation Report for NM_002435.3(MPI):c.845-2del]

NM_002435.3(MPI):c.845-2del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_002435.3(MPI):c.845-2del

HGVS:

NC_000015.10:g.74897009del
NG_008921.1:g.11941del
NG_008921.2:g.11969del
NM_001289155.2:c.845-503del
NM_001289156.2:c.695-2del
NM_001289157.2:c.662-2del
NM_001330372.2:c.785-2del
NM_002435.3:c.845-2delMANE SELECT
NC_000015.9:g.75189350del
NM_002435.1:c.845-2delA

Links:

dbSNP: rs1555479341

NCBI 1000 Genomes Browser:

rs1555479341

Molecular consequence:

NM_001289155.2:c.845-503del - intron variant - [Sequence Ontology: SO:0001627]
NM_001289156.2:c.695-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001289157.2:c.662-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001330372.2:c.785-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_002435.3:c.845-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793065	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Aug 1, 2017)	unknown	clinical testing	Citation Link,
SCV004616739	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 3, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 19862844, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793065

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Aug 1, 2017)

unknown

clinical testing

Citation Link,

SCV004616739

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 3, 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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000793065.1

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

#	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

From Invitae, SCV004616739.1

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

Description

This sequence change affects a splice site in intron 6 of the MPI gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MPI are known to be pathogenic (PMID: 19862844). This variant is not present in population databases (gnomAD no frequency). 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: 553083). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

Last Updated: Mar 5, 2024

ClinVar

Relating variation to medicine