NM_000528.4(MAN2B1):c.1420-27_1420-3del AND Deficiency of alpha-mannosidase

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Dec 27, 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:: RCV003112403.5

Allele description [Variation Report for NM_000528.4(MAN2B1):c.1420-27_1420-3del]

NM_000528.4(MAN2B1):c.1420-27_1420-3del

Gene:

MAN2B1:mannosidase alpha class 2B member 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_000528.4(MAN2B1):c.1420-27_1420-3del

HGVS:

NC_000019.10:g.12657060_12657084del
NG_008318.1:g.14695_14719del
NM_000528.4:c.1420-27_1420-3delMANE SELECT
NM_001173498.2:c.1417-27_1417-3del
NC_000019.9:g.12767873_12767897del
NC_000019.9:g.12767874_12767898del

Molecular consequence:

NM_000528.4:c.1420-27_1420-3del - intron variant - [Sequence Ontology: SO:0001627]
NM_001173498.2:c.1417-27_1417-3del - intron variant - [Sequence Ontology: SO:0001627]

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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Stigma-specific Stig1 family protein [Arabidopsis thaliana]
Stigma-specific Stig1 family protein [Arabidopsis thaliana]
gi|15219205|ref|NP_175721.1|

Protein
Gm12181 AND (alive[prop]) (2)
Gene
protein arginine N-methyltransferase 8 [Mus musculus]
protein arginine N-methyltransferase 8 [Mus musculus]
gi|357527369|ref|NP_958759.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003787153	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 27, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9915946, 28492532
SCV004191878	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 22, 2023)	unknown	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

SCV003787153

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 27, 2023)

germline

clinical testing

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

SCV004191878

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 22, 2023)

unknown

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	unknown	unknown	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

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

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, SCV003787153.3

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

Description

This sequence change falls in intron 11 of the MAN2B1 gene. It does not directly change the encoded amino acid sequence of the MAN2B1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with alpha mannosidosis (PMID: 9915946). This variant is also known as IVS11-3del25. ClinVar contains an entry for this variant (Variation ID: 2419159). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 9915946). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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 Baylor Genetics, SCV004191878.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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