NM_000528.4(MAN2B1):c.2887G>T (p.Glu963Ter) AND Deficiency of alpha-mannosidase

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 14, 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:: RCV001236147.7

Allele description [Variation Report for NM_000528.4(MAN2B1):c.2887G>T (p.Glu963Ter)]

NM_000528.4(MAN2B1):c.2887G>T (p.Glu963Ter)

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.2887G>T (p.Glu963Ter)

HGVS:

NC_000019.10:g.12647269C>A
NG_008318.1:g.24509G>T
NM_000528.4:c.2887G>TMANE SELECT
NM_001173498.2:c.2884G>T
NP_000519.2:p.Glu963Ter
NP_001166969.1:p.Glu962Ter
NC_000019.9:g.12758083C>A
NM_000528.3:c.2887G>T

Protein change:

E962*

Links:

dbSNP: rs757072948

NCBI 1000 Genomes Browser:

rs757072948

Molecular consequence:

NM_000528.4:c.2887G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001173498.2:c.2884G>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

Recent activity

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acyl-CoA thioesterase 2 [Klebsiella quasipneumoniae subsp. similipneumoniae]
acyl-CoA thioesterase 2 [Klebsiella quasipneumoniae subsp. similipneumoniae]
gi|555116113|gb|ESM59052.1||gnl|WGS |L390_04251T0

Protein
Enterobacter cloacae strain CH1 contig14, whole genome shotgun sequence
Enterobacter cloacae strain CH1 contig14, whole genome shotgun sequence
gi|821212792|gb|JSWZ01000014.1||gnl JSWZ01|contig14

Nucleotide
protein fantom isoform a [Homo sapiens]
protein fantom isoform a [Homo sapiens]
gi|118442834|ref|NP_056087.2|

Protein
Clitocella sp. voucher BJTC FM1952 ATP synthase subunit 6 (ATP6) gene, partial c...
Clitocella sp. voucher BJTC FM1952 ATP synthase subunit 6 (ATP6) gene, partial cds
gi|2226060985|gb|OL989926.1|

Nucleotide
Homo sapiens mRNA for Rh blood group, D antigen (RHD gene), isolate 43-2015, all...
Homo sapiens mRNA for Rh blood group, D antigen (RHD gene), isolate 43-2015, allele RHD R10L
gi|773554749|emb|LN824132.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001408860	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22161967, 28492532
SCV002014042	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001408860

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 14, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002014042

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 5, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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. doi: 10.1002/humu.23002.

PubMed [citation]

PMID:: 22161967

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001408860.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant disrupts a region of the MAN2B1 protein in which other variant(s) (p.Thr974Argfs*) have been determined to be pathogenic (PMID: 22161967). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 962313). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu963*) in the MAN2B1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 amino acid(s) of the MAN2B1 protein. For these reasons, this variant has been classified as 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

From Genome-Nilou Lab, SCV002014042.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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