NM_000528.4(MAN2B1):c.1066C>G (p.Pro356Ala) AND Deficiency of alpha-mannosidase

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 3, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002023650.5

Allele description [Variation Report for NM_000528.4(MAN2B1):c.1066C>G (p.Pro356Ala)]

NM_000528.4(MAN2B1):c.1066C>G (p.Pro356Ala)

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.1066C>G (p.Pro356Ala)

HGVS:

NC_000019.10:g.12658471G>C
NG_008318.1:g.13307C>G
NM_000528.4:c.1066C>GMANE SELECT
NM_001173498.2:c.1063C>G
NP_000519.2:p.Pro356Ala
NP_001166969.1:p.Pro355Ala
NC_000019.9:g.12769285G>C

Protein change:

P355A

Links:

dbSNP: rs2145262130

NCBI 1000 Genomes Browser:

rs2145262130

Molecular consequence:

NM_000528.4:c.1066C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001173498.2:c.1063C>G - missense variant - [Sequence Ontology: SO:0001583]

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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conserved hypothetical protein [Cryptococcus neoformans var. neoformans JEC21]
conserved hypothetical protein [Cryptococcus neoformans var. neoformans JEC21]
gi|57223965|gb|AAW42008.1||gnl|tigr CNB05740.1

Protein
similar to alpha-L-rhamnosidase [Plenodomus lingam JN3]
similar to alpha-L-rhamnosidase [Plenodomus lingam JN3]
gi|312220200|emb|CBY00141.1|

Protein
glycosyl hydrolase family 65 protein [Burkholderia oklahomensis]
glycosyl hydrolase family 65 protein [Burkholderia oklahomensis]
gi|497801623|ref|WP_010115807.1|

Protein
Klk13 kallikrein related-peptidase 13 [Rattus norvegicus]
Klk13 kallikrein related-peptidase 13 [Rattus norvegicus]
Gene ID:292848

Gene
292848[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002304686	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 3, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9758606, 15035660, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002304686

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 3, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.

Gotoda Y, Wakamatsu N, Kawai H, Nishida Y, Matsumoto T.

Am J Hum Genet. 1998 Oct;63(4):1015-24.

PubMed [citation]

PMID:: 9758606
PMCID:: PMC1377481

Intracellular transport of human lysosomal alpha-mannosidase and alpha-mannosidosis-related mutants.

Hansen G, Berg T, Riise Stensland HM, Heikinheimo P, Klenow H, Evjen G, Nilssen Ø, Tollersrud OK.

Biochem J. 2004 Jul 15;381(Pt 2):537-46.

PubMed [citation]

PMID:: 15035660
PMCID:: PMC1133862

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002304686.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Pro356 amino acid residue in MAN2B1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9758606, 15035660). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 356 of the MAN2B1 protein (p.Pro356Ala).

#	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

Last Updated: Sep 16, 2024

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