chr2-74464919-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_006302.3(MOGS):c.329G>A(p.Arg110His) variant causes a missense change. The variant allele was found at a frequency of 0.00000125 in 1,604,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. R110R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.07

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.83

PP5

Variant 2-74464919-C-T is Pathogenic according to our data. Variant chr2-74464919-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 217735.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3 link	c.329G>A	p.Arg110His	missense_variant	Exon 1 of 4	ENST00000448666.7	NP_006293.2	Q13724-1A0A384MDR6
MOGS	NM_001146158.2 link	c.11G>A	p.Arg4His	missense_variant	Exon 2 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.329G>A	p.Arg110His	missense_variant	Exon 1 of 4	1	NM_006302.3	ENSP00000410992.3		Q13724-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721048

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33366

American (AMR)

AF:

0.00

AC:

AN:

43532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25892

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39316

South Asian (SAS)

AF:

0.00

AC:

AN:

84760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107014

Other (OTH)

AF:

0.00

AC:

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MOGS-congenital disorder of glycosylation

Pathogenic:1

Mar 01, 2015

Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.069

T;T;T;.;.;.;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.94

.;D;D;D;D;D;D

M_CAP

Benign

0.044

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.1

M;M;.;.;.;.;.

PhyloP100

5.1

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.6

.;D;D;.;.;D;.

REVEL

Uncertain

0.53

Sift

Uncertain

0.0020

.;D;D;.;.;D;.

Sift4G

Uncertain

0.0040

.;D;D;.;.;D;.

Polyphen

1.0

D;D;.;.;.;.;.

Vest4

0.85, 0.96, 0.78

MVP

0.85

MPC

0.95

ClinPred

1.0

GERP RS

4.8

PromoterAI

-0.0014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.87

gMVP

0.95

Mutation Taster

=2/98

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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