chr2-74465163-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006302.3(MOGS):c.85C>G(p.Arg29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000496 in 1,530,734 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 6 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.448

Publications

3 publications found

Variant links:

Genes affected

MOGS (HGNC:24862): (mannosyl-oligosaccharide glucosidase) This gene encodes the first enzyme in the N-linked oligosaccharide processing pathway. The enzyme cleaves the distal alpha-1,2-linked glucose residue from the Glc(3)-Man(9)-GlcNAc(2) oligosaccharide precursor. This protein is located in the lumen of the endoplasmic reticulum. Defects in this gene are a cause of type IIb congenital disorder of glycosylation (CDGIIb). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

MOGS Gene-Disease associations (from GenCC):

MOGS-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

MOGS links:

ENSG00000286883 (HGNC:):

ENSG00000286883 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004206836).

BP6

Variant 2-74465163-G-C is Benign according to our data. Variant chr2-74465163-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 337114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000644 (98/152262) while in subpopulation EAS AF = 0.0153 (79/5168). AF 95% confidence interval is 0.0126. There are 0 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3 link	c.85C>G	p.Arg29Gly	missense_variant	Exon 1 of 4	ENST00000448666.7	NP_006293.2	Q13724-1A0A384MDR6
MOGS	NM_001146158.2 link	c.-59+151C>G		intron_variant	Intron 1 of 4		NP_001139630.1	Q13724-2Q58F09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7 link	c.85C>G	p.Arg29Gly	missense_variant	Exon 1 of 4	1	NM_006302.3	ENSP00000410992.3		Q13724-1

Frequencies

GnomAD3 genomes

AF:

0.000638

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00130

AC:

165

AN:

126576

AF XY:

0.00104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000416

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00207

GnomAD4 exome

AF:

0.000480

AC:

661

AN:

1378472

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

312

AN XY:

680504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30062

American (AMR)

AF:

0.0000283

AC:

AN:

35396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24764

East Asian (EAS)

AF:

0.0144

AC:

502

AN:

34828

South Asian (SAS)

AF:

0.0000381

AC:

AN:

78756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1077284

Other (OTH)

AF:

0.00264

AC:

152

AN:

57552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000644

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.000784

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0153

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000856

Hom.:

Bravo

AF:

0.000752

ExAC

AF:

0.000686

AC:

Asia WGS

AF:

0.0110

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MOGS-congenital disorder of glycosylation

Benign:2

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Aug 03, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

MOGS-related disorder

Benign:1

Sep 09, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MOGS: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0065

T;T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.54

.;T;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;.;.

PhyloP100

0.45

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.69

.;N;N;.;.

REVEL

Benign

0.050

Sift

Benign

0.074

.;T;D;.;.

Sift4G

Benign

0.38

.;T;T;.;.

Polyphen

0.0

B;B;.;.;.

Vest4

0.19, 0.18

MutPred

0.23

Loss of methylation at R29 (P = 0.0137);Loss of methylation at R29 (P = 0.0137);Loss of methylation at R29 (P = 0.0137);Loss of methylation at R29 (P = 0.0137);Loss of methylation at R29 (P = 0.0137);

MVP

0.22

MPC

0.30

ClinPred

0.013

GERP RS

0.72

PromoterAI

-0.091

Neutral

(source)

Varity_R

0.12

gMVP

0.75

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over