rs35533773

Positions:

chr2-74461436-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006302.3(MOGS):c.2353G>A(p.Gly785Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00872 in 1,614,216 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 56 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 97 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0310

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016371608).

BP6

Variant 2-74461436-C-T is Benign according to our data. Variant chr2-74461436-C-T is described in ClinVar as [Benign]. Clinvar id is 337104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0184 (2803/152362) while in subpopulation AFR AF= 0.0481 (2000/41574). AF 95% confidence interval is 0.0464. There are 56 homozygotes in gnomad4. There are 1324 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOGS	NM_006302.3 linkuse as main transcript	c.2353G>A	p.Gly785Ser	missense_variant	4/4	ENST00000448666.7
MOGS	NM_001146158.2 linkuse as main transcript	c.2035G>A	p.Gly679Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOGS	ENST00000448666.7 linkuse as main transcript	c.2353G>A	p.Gly785Ser	missense_variant	4/4	1	NM_006302.3	P1	Q13724-1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2793

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0480

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0105

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00664

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.00966

AC:

2411

AN:

249522

Hom.:

AF XY:

0.00965

AC XY:

1306

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.0458

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0134

Gnomad FIN exome

AF:

0.00325

Gnomad NFE exome

AF:

0.00640

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00771

AC:

11269

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00778

AC XY:

5658

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0474

Gnomad4 AMR exome

AF:

0.00402

Gnomad4 ASJ exome

AF:

0.0279

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0140

Gnomad4 FIN exome

AF:

0.00339

Gnomad4 NFE exome

AF:

0.00603

Gnomad4 OTH exome

AF:

0.00982

GnomAD4 genome

AF:

0.0184

AC:

2803

AN:

152362

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1324

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0481

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00664

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00893

Hom.:

Bravo

AF:

0.0195

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.0435

AC:

181

ESP6500EA

AF:

0.00820

AC:

ExAC

AF:

0.0106

AC:

1280

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00752

EpiControl

AF:

0.00545

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MOGS-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 06, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 22, 2016

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Oct 17, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.6

DANN

Benign

0.85

DEOGEN2

Benign

0.0027

T;T;.;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.24

.;T;.;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

N;N;.;.;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

1.4

.;N;.;.;N

REVEL

Benign

0.026

Sift

Benign

0.85

.;T;.;.;T

Sift4G

Benign

0.72

.;T;.;.;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.011, 0.021

MPC

0.23

ClinPred

0.00083

GERP RS

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over