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NM_000303.3(PMM2):c.584_585del (p.His195fs) AND PMM2-congenital disorder of glycosylation

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Feb 10, 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:
RCV003026962.4

Allele description [Variation Report for NM_000303.3(PMM2):c.584_585del (p.His195fs)]

NM_000303.3(PMM2):c.584_585del (p.His195fs)

Gene:
PMM2:phosphomannomutase 2 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
16p13.2
Genomic location:
Preferred name:
NM_000303.3(PMM2):c.584_585del (p.His195fs)
HGVS:
  • NC_000016.10:g.8813051_8813052del
  • NG_009209.1:g.20239_20240del
  • NM_000303.3:c.584_585delMANE SELECT
  • NP_000294.1:p.His195fs
  • NC_000016.9:g.8906908_8906909del
Protein change:
H195fs
Molecular consequence:
  • NM_000303.3:c.584_585del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003324108Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Mar 15, 2022)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV004205302Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Feb 10, 2023)
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

High residual activity of PMM2 in patients' fibroblasts: possible pitfall in the diagnosis of CDG-Ia (phosphomannomutase deficiency).

Grünewald S, Schollen E, Van Schaftingen E, Jaeken J, Matthijs G.

Am J Hum Genet. 2001 Feb;68(2):347-54. Epub 2001 Jan 11.

PubMed [citation]
PMID:
11156536
PMCID:
PMC1235268

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia.

Westphal V, Peterson S, Patterson M, Tournay A, Blumenthal A, Treacy EP, Freeze HH.

Genet Med. 2001 Nov-Dec;3(6):393-8.

PubMed [citation]
PMID:
11715002
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003324108.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PMM2 protein in which other variant(s) (p.Cys241Ser) have been determined to be pathogenic (PMID: 11156536, 11715002, 15844218, 21541725, 22012410, 25355454, 26014514). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with PMM2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His195Argfs*4) in the PMM2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the PMM2 protein.

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

From Baylor Genetics, SCV004205302.1

#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