U.S. flag

An official website of the United States government

NM_002435.3(MPI):c.487+2del AND MPI-congenital disorder of glycosylation

Germline classification:
Likely pathogenic (4 submissions)
Last evaluated:
Feb 21, 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:
RCV000410117.12

Allele description [Variation Report for NM_002435.3(MPI):c.487+2del]

NM_002435.3(MPI):c.487+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.487+2del
HGVS:
  • NC_000015.10:g.74892804del
  • NG_008921.1:g.7736del
  • NG_008921.2:g.7764del
  • NM_001289155.2:c.487+2del
  • NM_001289156.2:c.337+2del
  • NM_001289157.2:c.487+2del
  • NM_001330372.2:c.427+2del
  • NM_002435.3:c.487+2delMANE SELECT
  • NC_000015.9:g.75185145del
  • NM_002435.1:c.487+2delT
  • NM_002435.2:c.487+2del
  • NM_002435.2:c.487+2delT
Links:
dbSNP: rs1057516550
NCBI 1000 Genomes Browser:
rs1057516550
Molecular consequence:
  • NM_001289155.2:c.487+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001289156.2:c.337+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001289157.2:c.487+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001330372.2:c.427+2del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_002435.3:c.487+2del - splice donor variant - [Sequence Ontology: SO:0001575]

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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000485858Counsyl
criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))
Likely pathogenic
(Feb 22, 2016)
unknownclinical testing

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001223738Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Dec 9, 2023)
germlineclinical testing

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

SCV002089782Natera, Inc.
no assertion criteria provided
Likely pathogenic
(Jun 24, 2017)
germlineclinical testing

SCV004195526Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Feb 21, 2024)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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 (4)

Details of each submission

From Counsyl, SCV000485858.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001223738.5

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

Description

This sequence change affects a splice site in intron 4 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 present in population databases (no rsID available, 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: 370515). 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.

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

From Natera, Inc., SCV002089782.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV004195526.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024