NM_005908.4(MANBA):c.2296C>T (p.Arg766Trp) AND Beta-D-mannosidosis

Clinical significance:Uncertain significance (Last evaluated: Oct 31, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000380220.4

Allele description [Variation Report for NM_005908.4(MANBA):c.2296C>T (p.Arg766Trp)]

NM_005908.4(MANBA):c.2296C>T (p.Arg766Trp)

Gene:
MANBA:mannosidase beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q24
Genomic location:
Preferred name:
NM_005908.4(MANBA):c.2296C>T (p.Arg766Trp)
HGVS:
  • NC_000004.12:g.102634907G>A
  • NG_012804.1:g.131088C>T
  • NG_012804.2:g.131088C>T
  • NM_005908.4:c.2296C>TMANE SELECT
  • NP_005899.3:p.Arg766Trp
  • NC_000004.11:g.103556064G>A
  • NM_005908.3:c.2296C>T
Protein change:
R766W
Links:
dbSNP: rs147428514
NCBI 1000 Genomes Browser:
rs147428514
Molecular consequence:
  • NM_005908.4:c.2296C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Beta-D-mannosidosis (MANSB)
Synonyms:
Mannosidosis, beta A, lysosomal; Lysosomal beta-mannosidase deficiency; Beta-mannosidase deficiency
Identifiers:
MONDO: MONDO:0009562; MedGen: C4048196; Orphanet: 118; OMIM: 248510

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000446772Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jan 12, 2018)
germlineclinical testing

Citation Link,

SCV000828320Invitaecriteria provided, single submitter
Uncertain significance
(Feb 22, 2018)
germlineclinical testing

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

SCV000895603Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Uncertain significance
(Oct 31, 2018)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000446772.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000828320.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with tryptophan at codon 766 of the MANBA protein (p.Arg766Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs147428514, ExAC 0.05%). This variant has not been reported in the literature in individuals with MANBA-related disease. ClinVar contains an entry for this variant (Variation ID: 347083). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Fulgent Genetics,Fulgent Genetics, SCV000895603.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2021

Support Center