NM_000528.4(MAN2B1):c.241del (p.Val81fs) AND Deficiency of alpha-mannosidase

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 2, 2024
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:: RCV003461824.4

Allele description [Variation Report for NM_000528.4(MAN2B1):c.241del (p.Val81fs)]

NM_000528.4(MAN2B1):c.241del (p.Val81fs)

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.241del (p.Val81fs)

HGVS:

NC_000019.10:g.12665724del
NG_008318.1:g.6054del
NG_015814.1:g.3921del
NG_140450.1:g.464del
NG_140450.2:g.464del
NM_000528.4:c.241delMANE SELECT
NM_001173498.2:c.241del
NP_000519.2:p.Val81fs
NP_001166969.1:p.Val81fs
NC_000019.9:g.12776538del

Protein change:

V81fs

Molecular consequence:

NM_000528.4:c.241del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001173498.2:c.241del - 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

Recent activity

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Homo sapiens VPS33B late endosome and lysosome associated (VPS33B), RefSeqGene (...
Homo sapiens VPS33B late endosome and lysosome associated (VPS33B), RefSeqGene (LRG_884) on chromosome 15
gi|237874180|ref|NG_012162.1||gnl|L G_884

Nucleotide
Chain A, CUGBP Elav-like family member 1
Chain A, CUGBP Elav-like family member 1
gi|310689907|pdb|3NNA|A

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004191852	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 2, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004297900	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9915946, 22161967, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004191852

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 2, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004297900

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 13, 2023)

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
not provided	unknown	unknown	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

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

See all PubMed Citations (4)

Details of each submission

From Baylor Genetics, SCV004191852.2

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297900.1

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

Description

This sequence change creates a premature translational stop signal (p.Val81Trpfs*76) 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). This variant is present in population databases (rs746868162, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967). For these reasons, this variant has been classified as 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: Sep 29, 2024

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