2-74463251-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
MOGS	NM_006302.3	c.715G>A	p.Asp239Asn	missense_variant	3/4	ENST00000448666.7
MOGS	NM_001146158.2	c.397G>A	p.Asp133Asn	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOGS	ENST00000448666.7	c.715G>A	p.Asp239Asn	missense_variant	3/4	1	NM_006302.3	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51328 AN: 151896 Hom.: 14176 Cov.: 32

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

GnomAD3 exomes AF: 0.259 AC: 64736 AN: 249574 Hom.: 14512 AF XY: 0.247 AC XY: 33457 AN XY: 135404

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 SAS exome AF: 0.280

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.: 34 AF XY: 0.184 AC XY: 134024 AN XY: 727220

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.834

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.338 AC: 51411 AN: 152014 Hom.: 14204 Cov.: 32 AF XY: 0.338 AC XY: 25121 AN XY: 74284

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.293

Alfa AF: 0.180 Hom.: 9900

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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	Eurofins Ntd Llc (ga)	Jul 26, 2012	- -

MOGS-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0047	T;T;.;.;.;.
Eigen	Benign	-0.0075
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.51	D
MetaRNN	Benign	0.0000029	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L;.;.;.;.
MutationTaster	Benign	0.045	P;P;P;P
PrimateAI	Benign	0.43	T
REVEL	Benign	0.056
Polyphen		0.56	P;P;.;.;.;.
Vest4		0.11, 0.19
MPC		0.26
ClinPred		0.0071	T
GERP RS		4.8
Varity_R		0.18
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs1063588; hg19: chr2-74690378; COSMIC: COSV52028259; COSMIC: COSV52028259;