NM_006302.3(MOGS):c.65C>A (p.Ala22Glu) AND MOGS-congenital disorder of glycosylation

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 19, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001857297.4

Allele description [Variation Report for NM_006302.3(MOGS):c.65C>A (p.Ala22Glu)]

NM_006302.3(MOGS):c.65C>A (p.Ala22Glu)

Gene:

MOGS:mannosyl-oligosaccharide glucosidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_006302.3(MOGS):c.65C>A (p.Ala22Glu)

HGVS:

NC_000002.12:g.74465183G>T
NG_008922.1:g.5228C>A
NM_001146158.2:c.-59+131C>A
NM_006302.3:c.65C>AMANE SELECT
NP_006293.2:p.Ala22Glu
LRG_1226t1:c.65C>A
LRG_1226:g.5228C>A
LRG_1226p1:p.Ala22Glu
NC_000002.11:g.74692310G>T
NM_006302.2:c.65C>A

Protein change:

A22E

Links:

OMIM: 601336.0004; dbSNP: rs753961807

NCBI 1000 Genomes Browser:

rs753961807

Molecular consequence:

NM_001146158.2:c.-59+131C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_006302.3:c.65C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: MOGS-congenital disorder of glycosylation
Synonyms:: CDG IIb; GLUCOSIDASE I DEFICIENCY; Congenital disorder of glycosylation type 2B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011629; MedGen: C1853736; Orphanet: 79330; OMIM: 606056

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002216354	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26805780, 33261925, 28492532
SCV002787774	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 8, 2021)	unknown	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

SCV002216354

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002787774

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 8, 2021)

unknown

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

Citations

PubMed

Mitotic Intragenic Recombination: A Mechanism of Survival for Several Congenital Disorders of Glycosylation.

Kane MS, Davids M, Adams C, Wolfe LA, Cheung HW, Gropman A, Huang Y; NISC Comparative Sequencing Program, Ng BG, Freeze HH, Adams DR, Gahl WA, Boerkoel CF.

Am J Hum Genet. 2016 Feb 4;98(2):339-46. doi: 10.1016/j.ajhg.2015.12.007. Epub 2016 Jan 21.

PubMed [citation]

PMID:: 26805780
PMCID:: PMC4746335

Congenital disorders of glycosylation type IIb with MOGS mutations cause early infantile epileptic encephalopathy, dysmorphic features, and hepatic dysfunction.

Anzai R, Tsuji M, Yamashita S, Wada Y, Okamoto N, Saitsu H, Matsumoto N, Goto T.

Brain Dev. 2021 Mar;43(3):402-410. doi: 10.1016/j.braindev.2020.10.013. Epub 2020 Nov 28.

PubMed [citation]

PMID:: 33261925

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002216354.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 22 of the MOGS protein (p.Ala22Glu). This variant is present in population databases (rs753961807, gnomAD 0.009%). This missense change has been observed in individual(s) with congenital disorder of glycosylation (PMID: 26805780, 33261925). ClinVar contains an entry for this variant (Variation ID: 441235). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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

From Fulgent Genetics, Fulgent Genetics, SCV002787774.1

#	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

Last Updated: Sep 29, 2024

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