2-74463251-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006302.3(MOGS):c.715G>A(p.Asp239Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,613,850 control chromosomes in the GnomAD database, including 55,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 14204 hom., cov: 32)

Exomes 𝑓: 0.18 ( 41224 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.05

Publications

68 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 2-74463251-C-T is Benign according to our data. Variant chr2-74463251-C-T is described in ClinVar as Benign. ClinVar VariationId is 95362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3 link	c.715G>A	p.Asp239Asn	missense_variant	Exon 3 of 4	ENST00000448666.7	NP_006293.2	Q13724-1A0A384MDR6
MOGS	NM_001146158.2 link	c.397G>A	p.Asp133Asn	missense_variant	Exon 4 of 5		NP_001139630.1	Q13724-2Q58F09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7 link	c.715G>A	p.Asp239Asn	missense_variant	Exon 3 of 4	1	NM_006302.3	ENSP00000410992.3		Q13724-1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51328

AN:

151896

Hom.:

14176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.259

AC:

64736

AN:

249574

AF XY:

0.247

show subpopulations

Gnomad AFR exome

AF:

0.735

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.841

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.184

AC:

269080

AN:

1461836

Hom.:

41224

Cov.:

AF XY:

0.184

AC XY:

134024

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.739

AC:

24741

AN:

33478

American (AMR)

AF:

0.259

AC:

11605

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

3296

AN:

26136

East Asian (EAS)

AF:

0.834

AC:

33090

AN:

39700

South Asian (SAS)

AF:

0.278

AC:

23942

AN:

86252

European-Finnish (FIN)

AF:

0.140

AC:

7457

AN:

53412

Middle Eastern (MID)

AF:

0.181

AC:

1042

AN:

5768

European-Non Finnish (NFE)

AF:

0.135

AC:

150061

AN:

1111974

Other (OTH)

AF:

0.229

AC:

13846

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

12005

24009

36014

48018

60023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6016

12032

18048

24064

30080

<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:

0.338

AC:

51411

AN:

152014

Hom.:

14204

Cov.:

AF XY:

0.338

AC XY:

25121

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.719

AC:

29795

AN:

41452

American (AMR)

AF:

0.267

AC:

4070

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

428

AN:

3470

East Asian (EAS)

AF:

0.824

AC:

4250

AN:

5160

South Asian (SAS)

AF:

0.305

AC:

1472

AN:

4820

European-Finnish (FIN)

AF:

0.138

AC:

1456

AN:

10584

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9056

AN:

67960

Other (OTH)

AF:

0.293

AC:

617

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1202

2405

3607

4810

6012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.213

Hom.:

22169

Bravo

AF:

0.371

TwinsUK

AF:

0.138

AC:

511

ALSPAC

AF:

0.135

AC:

519

ESP6500AA

AF:

0.674

AC:

2661

ESP6500EA

AF:

0.136

AC:

1138

ExAC

AF:

0.267

AC:

32267

Asia WGS

AF:

0.571

AC:

1982

AN:

3478

EpiCase

AF:

0.138

EpiControl

AF:

0.142

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 02, 2015

GeneDx

Significance: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. -

Jul 26, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

MOGS-congenital disorder of glycosylation

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0047

T;T;.;.;.;.

Eigen

Benign

-0.0075

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.67

.;T;T;T;T;T

MetaRNN

Benign

0.0000029

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;.;.;.;.

PhyloP100

1.1

PrimateAI

Benign

0.43

PROVEAN

Benign

0.26

.;N;.;N;.;N

REVEL

Benign

0.056

Sift

Benign

0.41

.;T;.;T;.;T

Sift4G

Benign

0.72

.;T;.;T;.;T

Polyphen

0.56

P;P;.;.;.;.

Vest4

0.11, 0.19

MPC

0.26

ClinPred

0.0071

GERP RS

4.8

Varity_R

0.18

gMVP

0.53

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.34

Position offset: 3

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