NM_018297.4(NGLY1):c.659G>A (p.Gly220Asp) AND Congenital disorder of deglycosylation

Clinical significance:Uncertain significance (Last evaluated: Sep 17, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000693243.4

Allele description [Variation Report for NM_018297.4(NGLY1):c.659G>A (p.Gly220Asp)]

NM_018297.4(NGLY1):c.659G>A (p.Gly220Asp)

Gene:
NGLY1:N-glycanase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p24.2
Genomic location:
Preferred name:
NM_018297.4(NGLY1):c.659G>A (p.Gly220Asp)
HGVS:
  • NC_000003.12:g.25739799C>T
  • NG_034108.1:g.55241G>A
  • NM_001145293.2:c.659G>A
  • NM_001145294.2:c.533G>A
  • NM_001145295.2:c.659G>A
  • NM_018297.4:c.659G>AMANE SELECT
  • NP_001138765.1:p.Gly220Asp
  • NP_001138766.1:p.Gly178Asp
  • NP_001138767.1:p.Gly220Asp
  • NP_060767.2:p.Gly220Asp
  • NC_000003.11:g.25781290C>T
  • NC_000003.11:g.25781290C>T
  • NM_018297.3:c.659G>A
Protein change:
G178D
Links:
dbSNP: rs748862974
NCBI 1000 Genomes Browser:
rs748862974
Molecular consequence:
  • NM_001145293.2:c.659G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145294.2:c.533G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145295.2:c.659G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018297.4:c.659G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital disorder of deglycosylation (CDDG)
Synonyms:
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Iv
Identifiers:
MONDO: MONDO:0014109; MedGen: C3808991; Orphanet: 404454; OMIM: 615273

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000821103Invitaecriteria provided, single submitter
Uncertain significance
(Sep 17, 2019)
germlineclinical testing

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

SCV000897084Fulgent 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 providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot 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 Invitae, SCV000821103.3

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

Description

This sequence change replaces glycine with aspartic acid at codon 220 of the NGLY1 protein (p.Gly220Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs748862974, ExAC 0.02%). This variant has not been reported in the literature in individuals with NGLY1-related disease. 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 tolerated, 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, SCV000897084.1

#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: Oct 24, 2021

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