2-74461951-C-T

Position:

chr2-74461951-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.1838G>A(p.Arg613Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00848 in 1,614,114 control chromosomes in the GnomAD database, including 65 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R613W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0064 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 63 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.440

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=0.014911711).

BP6

Variant 2-74461951-C-T is Benign according to our data. Variant chr2-74461951-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 95358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00637 (970/152284) while in subpopulation NFE AF= 0.00916 (623/68018). AF 95% confidence interval is 0.00856. There are 2 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOGS	NM_006302.3 linkuse as main transcript	c.1838G>A	p.Arg613Gln	missense_variant	4/4	ENST00000448666.7
MOGS	NM_001146158.2 linkuse as main transcript	c.1520G>A	p.Arg507Gln	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOGS	ENST00000448666.7 linkuse as main transcript	c.1838G>A	p.Arg613Gln	missense_variant	4/4	1	NM_006302.3	P1	Q13724-1

Frequencies

GnomAD3 genomes

AF:

0.00637

AC:

970

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00916

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00679

AC:

1693

AN:

249446

Hom.:

AF XY:

0.00665

AC XY:

900

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00573

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00288

Gnomad FIN exome

AF:

0.00418

Gnomad NFE exome

AF:

0.00952

Gnomad OTH exome

AF:

0.00792

GnomAD4 exome

AF:

0.00870

AC:

12717

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00855

AC XY:

6219

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00651

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.00406

Gnomad4 NFE exome

AF:

0.00979

Gnomad4 OTH exome

AF:

0.00866

GnomAD4 genome

AF:

0.00637

AC:

970

AN:

152284

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

474

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00372

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00916

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00989

Hom.:

Bravo

AF:

0.00652

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00211

AC:

ESP6500EA

AF:

0.0112

AC:

ExAC

AF:

0.00666

AC:

807

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.00954

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 12, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 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. -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Nov 16, 2015	- -

MOGS-congenital disorder of glycosylation

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 12, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 17, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	MOGS: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.091

DANN

Benign

0.83

DEOGEN2

Benign

0.0054

T;T;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.64

.;T;.;T;T

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.88

.;N;.;.;N

REVEL

Benign

0.050

Sift

Benign

0.99

.;T;.;.;T

Sift4G

Benign

0.47

.;T;.;.;T

Polyphen

0.0070

B;B;.;.;.

Vest4

0.055, 0.056

MVP

0.20

MPC

0.27

ClinPred

0.0040

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.017

gMVP

0.26

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