NM_000528.4(MAN2B1):c.2437-300_2719del AND Deficiency of alpha-mannosidase

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 17, 2019
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:: RCV001041850.1

Allele description [Variation Report for NM_000528.4(MAN2B1):c.2437-300_2719del]

NM_000528.4(MAN2B1):c.2437-300_2719del

Genes:

LOC130063648:ATAC-STARR-seq lymphoblastoid active region 14063 [Gene]
LOC130063649:ATAC-STARR-seq lymphoblastoid silent region 10155 [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.2437-300_2719del

HGVS:

NC_000019.10:g.12647544_12648702del
NC_000019.10:g.12647547_12648705del
NG_008318.1:g.23076_24234del
NM_000528.4:c.2437-300_2719delMANE SELECT
NM_001173498.2:c.2434-300_2716del
NC_000019.9:g.12758361_12759519del
NM_000528.3:c.2437-300_2719del

Molecular consequence:

NM_000528.4:c.2437-300_2719del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001173498.2:c.2434-300_2716del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_000528.4:c.2437-300_2719del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001173498.2:c.2434-300_2716del - splice donor variant - [Sequence Ontology: SO:0001575]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001205496	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 17, 2019)	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

SCV001205496

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 17, 2019)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Details of each submission

From Invitae, SCV001205496.1

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

Description

This variant results in the deletion of exon 21 and part of exon 22 (c.2437-300_2719del) of the MAN2B1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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). 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

Last Updated: Oct 14, 2023

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