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NM_000303.3(PMM2):c.391C>G (p.Pro131Ala) AND PMM2-congenital disorder of glycosylation

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Nov 19, 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:
RCV003064317.4

Allele description [Variation Report for NM_000303.3(PMM2):c.391C>G (p.Pro131Ala)]

NM_000303.3(PMM2):c.391C>G (p.Pro131Ala)

Gene:
PMM2:phosphomannomutase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.2
Genomic location:
Preferred name:
NM_000303.3(PMM2):c.391C>G (p.Pro131Ala)
HGVS:
  • NC_000016.10:g.8811122C>G
  • NG_009209.1:g.18310C>G
  • NM_000303.2:c.391C>G
  • NM_000303.3:c.391C>GMANE SELECT
  • NP_000294.1:p.Pro131Ala
  • NC_000016.9:g.8904979C>G
  • NM_000303.3:c.391C>G
Protein change:
P131A
Molecular consequence:
  • NM_000303.3:c.391C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
PMM2-congenital disorder of glycosylation
Synonyms:
CDG Ia; JAEKEN SYNDROME; PHOSPHOMANNOMUTASE 2 DEFICIENCY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008907; MedGen: C0349653; Orphanet: 79318; OMIM: 212065

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003441817Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jun 28, 2022)
germlineclinical testing

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

SCV005056377Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Nov 19, 2023)
unknownclinical testing

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

Summary from all submissions

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

Citations

PubMed

Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome).

Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, Van Schaftingen E.

Nat Genet. 1997 May;16(1):88-92. Erratum in: Nat Genet 1997 Jul;16(3):316.

PubMed [citation]
PMID:
9140401

A new insight into PMM2 mutations in the French population.

Le Bizec C, Vuillaumier-Barrot S, Barnier A, Dupré T, Durand G, Seta N.

Hum Mutat. 2005 May;25(5):504-5.

PubMed [citation]
PMID:
15844218
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003441817.2

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with PMM2-related conditions (PMID: 9140401, 15844218; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.06%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 131 of the PMM2 protein (p.Pro131Ala).

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

From Baylor Genetics, SCV005056377.1

#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: Jan 13, 2025