2-74461772-C-T

Position:

chr2-74461772-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.2017G>A(p.Val673Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,216 control chromosomes in the GnomAD database, including 154 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 0.0098 ( 17 hom., cov: 33)

Exomes 𝑓: 0.011 ( 137 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.23

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:

MOGS (HGNC:):

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=0.005691737).

BP6

Variant 2-74461772-C-T is Benign according to our data. Variant chr2-74461772-C-T is described in ClinVar as [Benign]. Clinvar id is 218681.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 = 0.00983 (1498/152338) while in subpopulation NFE AF= 0.0125 (852/68036). AF 95% confidence interval is 0.0118. There are 17 homozygotes in gnomad4. There are 771 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOGS	NM_006302.3 linkuse as main transcript	c.2017G>A	p.Val673Ile	missense_variant	4/4	ENST00000448666.7	NP_006293.2	Q13724-1A0A384MDR6
MOGS	NM_001146158.2 linkuse as main transcript	c.1699G>A	p.Val567Ile	missense_variant	5/5		NP_001139630.1	Q13724-2Q58F09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7 linkuse as main transcript	c.2017G>A	p.Val673Ile	missense_variant	4/4	1	NM_006302.3	ENSP00000410992.3		Q13724-1

Frequencies

GnomAD3 genomes

AF:

0.00985

AC:

1499

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0327

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0112

AC:

2800

AN:

249470

Hom.:

AF XY:

0.0115

AC XY:

1551

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00565

Gnomad FIN exome

AF:

0.0355

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0109

AC:

15944

AN:

1461878

Hom.:

137

Cov.:

AF XY:

0.0110

AC XY:

8013

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00616

Gnomad4 FIN exome

AF:

0.0351

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.00983

AC:

1498

AN:

152338

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

771

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.0237

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0327

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.00756

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00231

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.0107

AC:

1291

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 19, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 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. -

MOGS-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 02, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	MOGS: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0041

T;T;.;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.66

.;T;.;T;T

MetaRNN

Benign

0.0057

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.17

.;N;.;.;N

REVEL

Benign

0.043

Sift

Benign

0.41

.;T;.;.;T

Sift4G

Benign

0.42

.;T;.;.;T

Polyphen

0.071

B;B;.;.;.

Vest4

0.032, 0.047

MPC

0.20

ClinPred

0.0024

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.30

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