NM_000528.4(MAN2B1):c.2782G>C (p.Gly928Arg) AND Deficiency of alpha-mannosidase

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Jan 25, 2024
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:: RCV000415194.15

Allele description [Variation Report for NM_000528.4(MAN2B1):c.2782G>C (p.Gly928Arg)]

NM_000528.4(MAN2B1):c.2782G>C (p.Gly928Arg)

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.2782G>C (p.Gly928Arg)

HGVS:

NC_000019.10:g.12647481C>G
NG_008318.1:g.24297G>C
NM_000528.4:c.2782G>CMANE SELECT
NM_001173498.2:c.2779G>C
NP_000519.2:p.Gly928Arg
NP_001166969.1:p.Gly927Arg
NC_000019.9:g.12758295C>G
NM_000528.3:c.2782G>C

Protein change:

G927R

Links:

dbSNP: rs754733253

NCBI 1000 Genomes Browser:

rs754733253

Molecular consequence:

NM_000528.4:c.2782G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001173498.2:c.2779G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000328771	Baylor Genetics	no assertion criteria provided	Uncertain significance (Oct 3, 2014)	maternal, germline	clinical testing
SCV000794526	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Sep 28, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001051716	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 25, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002014524	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002086893	Natera, Inc.	no assertion criteria provided	Benign (Jan 28, 2020)	germline	clinical testing

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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	unknown	unknown	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
Hispanic Americans	maternal	yes	1	1	not provided	not provided	not provided	clinical testing
Hispanic Americans	germline	unknown	9	9	not provided	not provided	not provided	clinical testing

Citations

PubMed

Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.

Posey JE, Harel T, Liu P, Rosenfeld JA, James RA, Coban Akdemir ZH, Walkiewicz M, Bi W, Xiao R, Ding Y, Xia F, Beaudet AL, Muzny DM, Gibbs RA, Boerwinkle E, Eng CM, Sutton VR, Shaw CA, Plon SE, Yang Y, Lupski JR.

N Engl J Med. 2017 Jan 5;376(1):21-31. doi: 10.1056/NEJMoa1516767. Epub 2016 Dec 7.

PubMed [citation]

PMID:: 27959697
PMCID:: PMC5335876

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 Baylor Genetics, SCV000328771.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Hispanic Americans	1	not provided	not provided	clinical testing (GTR000508680.4)	not provided
2	Hispanic Americans	9	not provided	not provided	clinical testing (GTR000508680.4)	not provided

Description

Our laboratory reported dual molecular diagnoses in SCN8A (NM_014191.3, c.647T>G) and MAN2B1 (NM_000528.3, c.2782G>C and c.1383C>G in trans) in one individual with reported features that include delayed motor milestones, delayed speech, intellectual disability, hypotonia, seizure disorder (refractory epilepsy), abnormal movements (dyskinesia), minor dysmorphic features (flat nasal bridge, prominent eyes, full lips), microcephaly, dysphagia, and cortical visual impairment. Heterozygotes for the MAN2B1 variants would be expected to be asymptomatic carriers.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided	(GTR000508680.4)	1	not provided	1	not provided
2	germline	unknown	not provided	not provided	not provided	(GTR000508680.4)	9	not provided	9	not provided

From Counsyl, SCV000794526.1

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001051716.6

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002014524.1

#	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

From Natera, Inc., SCV002086893.1

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

#	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: Oct 13, 2024

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