NM_018297.4(NGLY1):c.1764_1785del (p.Asp588fs) AND Congenital disorder of deglycosylation

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 29, 2023
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:: RCV003741278.2

Allele description [Variation Report for NM_018297.4(NGLY1):c.1764_1785del (p.Asp588fs)]

NM_018297.4(NGLY1):c.1764_1785del (p.Asp588fs)

Gene:

NGLY1:N-glycanase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p24.2

Genomic location:

Preferred name:

NM_018297.4(NGLY1):c.1764_1785del (p.Asp588fs)

HGVS:

NC_000003.12:g.25720019_25720040del
NG_034108.1:g.75001_75022del
NM_001145293.2:c.1710_1731del
NM_001145294.2:c.1638_1659del
NM_001145295.2:c.1612-404_1612-383del
NM_018297.4:c.1764_1785delMANE SELECT
NP_001138765.1:p.Asp570fs
NP_001138766.1:p.Asp546fs
NP_060767.2:p.Asp588fs
NC_000003.11:g.25761509_25761530del
NC_000003.11:g.25761510_25761531del

Protein change:

D546fs

Links:

dbSNP: rs2125442722

NCBI 1000 Genomes Browser:

rs2125442722

Molecular consequence:

NM_001145293.2:c.1710_1731del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001145294.2:c.1638_1659del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018297.4:c.1764_1785del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001145295.2:c.1612-404_1612-383del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Congenital disorder of deglycosylation (CDDG)
Identifiers:: MONDO: MONDO:0031376; MedGen: C3808991; OMIM: PS615273

Recent activity

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Hap3p [Saccharomyces cerevisiae S288C]
Hap3p [Saccharomyces cerevisiae S288C]
gi|6319450|ref|NP_009532.1|

Protein
cytochrome oxidase subunit 1, partial (mitochondrion) [Ichneumonidae sp. BIOUG02...
cytochrome oxidase subunit 1, partial (mitochondrion) [Ichneumonidae sp. BIOUG02837-B04]
gi|1488058717|gb|AYG89755.1|

Protein
cytochrome oxidase subunit I, partial (mitochondrion) [Dasya sp.]
cytochrome oxidase subunit I, partial (mitochondrion) [Dasya sp.]
gi|2211765873|gb|UNS48937.1|

Protein
Vibrio 16S ribosomal RNA gene, partial sequence.
Vibrio 16S ribosomal RNA gene, partial sequence.
PopSet: 1153219874

PopSet
Gammaproteobacteria endonuclease I precursor, gene, complete cds.
Gammaproteobacteria endonuclease I precursor, gene, complete cds.
PopSet: 82394525

PopSet

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004552845	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24651605, 25900930, 30740912, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004552845

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 29, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway.

Enns GM, Shashi V, Bainbridge M, Gambello MJ, Zahir FR, Bast T, Crimian R, Schoch K, Platt J, Cox R, Bernstein JA, Scavina M, Walter RS, Bibb A, Jones M, Hegde M, Graham BH, Need AC, Oviedo A, Schaaf CP, Boyle S, Butte AJ, et al.

Genet Med. 2014 Oct;16(10):751-8. doi: 10.1038/gim.2014.22. Epub 2014 Mar 20. Erratum in: Genet Med. 2014 Jul;16(7):568. Chen, Rui [added].

PubMed [citation]

PMID:: 24651605
PMCID:: PMC4243708

A congenital disorder of deglycosylation: Biochemical characterization of N-glycanase 1 deficiency in patient fibroblasts.

He P, Grotzke JE, Ng BG, Gunel M, Jafar-Nejad H, Cresswell P, Enns GM, Freeze HH.

Glycobiology. 2015 Aug;25(8):836-44. doi: 10.1093/glycob/cwv024. Epub 2015 Apr 21.

PubMed [citation]

PMID:: 25900930
PMCID:: PMC4487302

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004552845.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Asp588Glufs*24) in the NGLY1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 67 amino acid(s) of the NGLY1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NGLY1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1324809). This variant disrupts a region of the NGLY1 protein in which other variant(s) (p.Gln631Serfs*7) have been determined to be pathogenic (PMID: 24651605, 25900930, 30740912). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Nov 10, 2024

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