NM_000528.4(MAN2B1):c.2920dup (p.Thr974fs) AND Deficiency of alpha-mannosidase

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 1, 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:: RCV001872910.5

Allele description [Variation Report for NM_000528.4(MAN2B1):c.2920dup (p.Thr974fs)]

NM_000528.4(MAN2B1):c.2920dup (p.Thr974fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_000528.4(MAN2B1):c.2920dup (p.Thr974fs)

HGVS:

NC_000019.10:g.12647236dup
NG_008318.1:g.24542dup
NM_000528.4:c.2920dupMANE SELECT
NM_001173498.2:c.2917dup
NP_000519.2:p.Thr974fs
NP_001166969.1:p.Thr973fs
NC_000019.9:g.12758049_12758050insT
NC_000019.9:g.12758050dup

Protein change:

T973fs

Links:

dbSNP: rs774791244

NCBI 1000 Genomes Browser:

rs774791244

Molecular consequence:

NM_000528.4:c.2920dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001173498.2:c.2917dup - 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

Clear Turn Off Turn On

SAMN32650287 (1)
SRA
ankyrin repeat domain-containing protein 10 isoform 1 [Homo sapiens]
ankyrin repeat domain-containing protein 10 isoform 1 [Homo sapiens]
gi|70995241|ref|NP_060134.2|

Protein
beta-1,4-galactosyltransferase 6 isoform X1 [Homo sapiens]
beta-1,4-galactosyltransferase 6 isoform X1 [Homo sapiens]
gi|2462561988|ref|XP_054175342.1|

Protein
hypothetical protein AGABI2DRAFT_120952 [Agaricus bisporus var. bisporus H97]
hypothetical protein AGABI2DRAFT_120952 [Agaricus bisporus var. bisporus H97]
gi|568465234|ref|XP_006464175.1||gn _WGS:AEOK|AGABI2DRAFT_120952

Protein
Arrestin C-terminal-like domain-containing protein [Caenorhabditis elegans]
Arrestin C-terminal-like domain-containing protein [Caenorhabditis elegans]
gi|392898412|ref|NP_500160.2|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002144099	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22161967, 28492532
SCV002807585	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 13, 2022)	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

SCV002144099

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2022)

germline

clinical testing

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

SCV002807585

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 13, 2022)

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	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

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002144099.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant results in an extension of the MAN2B1 protein. Other variant(s) that result in a similarly extended protein product (p.Thr974Argfs*?) have been determined to be pathogenic (PMID: 22161967). This suggests that these extensions are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1372339). This frameshift has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967). This variant is present in population databases (rs774791244, gnomAD 0.006%). This sequence change results in a frameshift in the MAN2B1 gene (p.Thr974Asnfs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the MAN2B1 protein and extend the protein by an uncertain number of additional amino acid residues.

#	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 Fulgent Genetics, Fulgent Genetics, SCV002807585.1

#	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 29, 2024

ClinVar

Relating variation to medicine