NM_000528.4(MAN2B1):c.164G>T (p.Cys55Phe) AND Deficiency of alpha-mannosidase

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Sep 27, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000206911.6

Allele description [Variation Report for NM_000528.4(MAN2B1):c.164G>T (p.Cys55Phe)]

NM_000528.4(MAN2B1):c.164G>T (p.Cys55Phe)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_000528.4(MAN2B1):c.164G>T (p.Cys55Phe)

HGVS:

NC_000019.10:g.12665801C>A
NG_008318.1:g.5977G>T
NG_015814.1:g.3998C>A
NM_000528.4:c.164G>TMANE SELECT
NM_001173498.2:c.164G>T
NP_000519.2:p.Cys55Phe
NP_001166969.1:p.Cys55Phe
NC_000019.9:g.12776615C>A
NM_000528.3:c.164G>T
O00754:p.Cys55Phe

Protein change:

C55F

Links:

UniProtKB: O00754#VAR_068034; dbSNP: rs864621975

NCBI 1000 Genomes Browser:

rs864621975

Molecular consequence:

NM_000528.4:c.164G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001173498.2:c.164G>T - missense variant - [Sequence Ontology: SO:0001583]

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 snail family transcriptional repressor 2 (SNAI2), mRNA
Homo sapiens snail family transcriptional repressor 2 (SNAI2), mRNA
gi|1519312066|ref|NM_003068.5|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000243955	ClinVar Staff, National Center for Biotechnology Information (NCBI)	no assertion criteria provided	Uncertain significance (Jun 7, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV003443118	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21505070, 22161967, 28492532
SCV004191916	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 27, 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

SCV000243955

ClinVar Staff, National Center for Biotechnology Information (NCBI)

no assertion criteria provided

Uncertain significance
(Jun 7, 2012)

germline

literature only

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

Citation Link,

SCV003443118

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 13, 2022)

germline

clinical testing

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

SCV004191916

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 27, 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	yes	not provided	not provided	not provided	not provided	not provided	literature only
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

Molecular and cellular characterization of novel {alpha}-mannosidosis mutations.

Kuokkanen E, Riise Stensland HM, Smith W, Kjeldsen Buvang E, Van Nguyen L, Nilssen Ø, Heikinheimo P.

Hum Mol Genet. 2011 Jul 1;20(13):2651-61. doi: 10.1093/hmg/ddr167. Epub 2011 Apr 19.

PubMed [citation]

PMID:: 21505070

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 ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000243955.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443118.2

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

Description

Experimental studies have shown that this missense change affects MAN2B1 function (PMID: 21505070, 22161967). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 208250). This missense change has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 55 of the MAN2B1 protein (p.Cys55Phe).

#	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 Baylor Genetics, SCV004191916.1

#	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

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