NM_000528.4(MAN2B1):c.2047A>G (p.Thr683Ala) AND Deficiency of alpha-mannosidase

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 27, 2022
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:: RCV003077214.2

Allele description [Variation Report for NM_000528.4(MAN2B1):c.2047A>G (p.Thr683Ala)]

NM_000528.4(MAN2B1):c.2047A>G (p.Thr683Ala)

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.2047A>G (p.Thr683Ala)

HGVS:

NC_000019.10:g.12650222T>C
NG_008318.1:g.21556A>G
NM_000528.3:c.2047A>G
NM_000528.4:c.2047A>GMANE SELECT
NM_001173498.2:c.2044A>G
NP_000519.2:p.Thr683Ala
NP_001166969.1:p.Thr682Ala
NC_000019.9:g.12761036T>C

Protein change:

T682A

Molecular consequence:

NM_000528.4:c.2047A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001173498.2:c.2044A>G - 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

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PREDICTED: Gymnodraco acuticeps kirre like nephrin family adhesion molecule 3a (...
PREDICTED: Gymnodraco acuticeps kirre like nephrin family adhesion molecule 3a (kirrel3a), transcript variant X1, mRNA
gi|1839639609|ref|XM_034226819.1|

Nucleotide
14086[uid] AND (alive[prop]) (1)
Gene
Fscn1 fascin actin-bundling protein 1 [Mus musculus]
Fscn1 fascin actin-bundling protein 1 [Mus musculus]
Gene ID:14086

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003456096	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 27, 2022)	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

SCV003456096

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 27, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003456096.1

#	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 replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 683 of the MAN2B1 protein (p.Thr683Ala). This variant is present in population databases (rs746776449, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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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