NM_000528.4(MAN2B1):c.2748_2751del (p.Leu917fs) AND Deficiency of alpha-mannosidase

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 13, 2022
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:: RCV001387084.7

Allele description [Variation Report for NM_000528.4(MAN2B1):c.2748_2751del (p.Leu917fs)]

NM_000528.4(MAN2B1):c.2748_2751del (p.Leu917fs)

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.2748_2751del (p.Leu917fs)

HGVS:

NC_000019.10:g.12647513_12647516del
NG_008318.1:g.24263_24266del
NM_000528.4:c.2748_2751delMANE SELECT
NM_001173498.2:c.2745_2748del
NP_000519.2:p.Leu917fs
NP_001166969.1:p.Leu916fs
NC_000019.9:g.12758326_12758329del
NC_000019.9:g.12758327_12758330del

Protein change:

L916fs

Links:

dbSNP: rs2145221516

NCBI 1000 Genomes Browser:

rs2145221516

Molecular consequence:

NM_000528.4:c.2748_2751del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001173498.2:c.2745_2748del - frameshift variant - [Sequence Ontology: SO:0001589]

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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RecName: Full=Angiopoietin-2; Short=ANG-2; Flags: Precursor
RecName: Full=Angiopoietin-2; Short=ANG-2; Flags: Precursor
gi|46577675|sp|O35608.2|ANGP2_MOUSE

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587579	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9915946, 22161967, 28492532
SCV002014375	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

SCV001587579

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 13, 2022)

germline

clinical testing

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

SCV002014375

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

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. doi: 10.1002/humu.23002.

PubMed [citation]

PMID:: 22161967

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001587579.4

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

Description

ClinVar contains an entry for this variant (Variation ID: 1073941). For these reasons, this variant has been classified as Pathogenic. 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.Leu917Serfs*6) in the MAN2B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967).

#	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, SCV002014375.1

#	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 29, 2024

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