2-74465236-G-A

Variant names:

• chr2-74465236-G-A
• NM_006302.3:c.12C>T
• MOGS p.Gly4Gly

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006302.3(MOGS):​c.12C>T​(p.Gly4Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G4G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MOGS NM_006302.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet, G2P

ENSG00000286883 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006302.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGS	NM_006302.3	MANE Select	c.12C>T	p.Gly4Gly	synonymous	Exon 1 of 4	NP_006293.2	A0A384MDR6
	MOGS	NM_001146158.2		c.-59+78C>T		intron	N/A	NP_001139630.1	Q13724-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGS	ENST00000448666.7	TSL:1 MANE Select	c.12C>T	p.Gly4Gly	synonymous	Exon 1 of 4	ENSP00000410992.3	Q13724-1
	MOGS	ENST00000452063.7	TSL:1	c.-59+78C>T		intron	N/A	ENSP00000388201.2	Q13724-2
	MOGS	ENST00000690565.1		c.12C>T	p.Gly4Gly	synonymous	Exon 1 of 5	ENSP00000510501.1	A0A8I5KTK5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1290604 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 636184

African (AFR) AF: 0.00 AC: 0 AN: 25872

American (AMR) AF: 0.00 AC: 0 AN: 18270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17940

East Asian (EAS) AF: 0.00 AC: 0 AN: 32434

South Asian (SAS) AF: 0.00 AC: 0 AN: 61078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045928

Other (OTH) AF: 0.00 AC: 0 AN: 53246

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.96
PhyloP100		0.053
PromoterAI		0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.68		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.68		Position offset: 2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-74692363;