NM_000528.4(MAN2B1):c.162del (p.Cys55fs) AND Deficiency of alpha-mannosidase

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 12, 2021
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:: RCV002221412.2

Allele description [Variation Report for NM_000528.4(MAN2B1):c.162del (p.Cys55fs)]

NM_000528.4(MAN2B1):c.162del (p.Cys55fs)

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.162del (p.Cys55fs)

HGVS:

NC_000019.10:g.12665803del
NG_008318.1:g.5975del
NG_015814.1:g.4000del
NM_000528.4:c.162delMANE SELECT
NM_001173498.2:c.162del
NP_000519.2:p.Cys55fs
NP_001166969.1:p.Cys55fs
NC_000019.9:g.12776617del
NM_000528.4:c.162delAMANE SELECT

Protein change:

C55fs

Links:

dbSNP: rs2145290970

NCBI 1000 Genomes Browser:

rs2145290970

Molecular consequence:

NM_000528.4:c.162del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001173498.2:c.162del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002498677	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 12, 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

SCV002498677

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 12, 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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Molecular Genetics, Royal Melbourne Hospital, SCV002498677.2

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

Description

This sequence change is a deletion of 1 bp in exon 2 (of 24) of MAN2B1 that is predicted to create a premature termination codon at position 63 (p.(Cys55Alafs*9)). It is expected to result in nonsense mediated decay in a gene where loss of function is an established mechanism of disease (ClinGen). The variant is absent in a large population cohort (gnomAD v2.1 and v3.1), and has not been reported in the relevant medical literature and databases. Based on the classification scheme RMH Modified ACMG Guidelines v1.3.2, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting.

#	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

ClinVar

Relating variation to medicine