NM_000528.4(MAN2B1):c.1954G>T (p.Glu652Ter) AND Deficiency of alpha-mannosidase

Clinical significance:Pathogenic (Last evaluated: Aug 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001038590.3

Allele description [Variation Report for NM_000528.4(MAN2B1):c.1954G>T (p.Glu652Ter)]

NM_000528.4(MAN2B1):c.1954G>T (p.Glu652Ter)

Gene:
MAN2B1:mannosidase alpha class 2B member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.13
Genomic location:
Preferred name:
NM_000528.4(MAN2B1):c.1954G>T (p.Glu652Ter)
HGVS:
  • NC_000019.10:g.12652245C>A
  • NG_008318.1:g.19533G>T
  • NM_000528.4:c.1954G>TMANE SELECT
  • NM_001173498.1:c.1951G>T
  • NP_000519.2:p.Glu652Ter
  • NP_001166969.1:p.Glu651Ter
  • NC_000019.9:g.12763059C>A
  • NM_000528.3:c.1954G>T
Protein change:
E651*
Molecular consequence:
  • NM_000528.4:c.1954G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001173498.1:c.1951G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Deficiency of alpha-mannosidase (MANSA)
Synonyms:
Lysosomal alpha-D-mannosidase deficiency; Alpha mannosidase B deficiency; Mannosidosis, alpha B lysosomal; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009561; MedGen: C0024748; Orphanet: 61; OMIM: 248500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001202068Invitaecriteria provided, single submitter
Pathogenic
(Aug 7, 2020)
germlineclinical testing

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

SCV001442226Myriad Women's Health, Inc.no assertion criteria provided
Likely pathogenic
(Dec 25, 2019)
unknownclinical testing

Citation Link

Description

NM_000528.3(MAN2B1):c.1954G>T(E652*) is expected to be pathogenic in the context of alpha-mannosidosis. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in MAN2B1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.

SCV001442226

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

Spectrum of mutations in alpha-mannosidosis.

Berg T, Riise HM, Hansen GM, Malm D, Tranebjaerg L, Tollersrud OK, Nilssen O.

Am J Hum Genet. 1999 Jan;64(1):77-88.

PubMed [citation]
PMID:
9915946
PMCID:
PMC1377705

Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.

Riise Stensland HM, Klenow HB, Van Nguyen L, Hansen GM, Malm D, Nilssen Ø.

Hum Mutat. 2012 Mar;33(3):511-20. doi: 10.1002/humu.22005. Epub 2012 Jan 23. Erratum in: Hum Mutat. 2016 Aug;37(8):827.

PubMed [citation]
PMID:
22161967
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001202068.2

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

Description

This sequence change creates a premature translational stop signal (p.Glu652*) in the MAN2B1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MAN2B1-related conditions. Loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967). For these reasons, this variant has been classified as Pathogenic.

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

From Myriad Women's Health, Inc., SCV001442226.1

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

Last Updated: May 10, 2021

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