chr2-74465163-G-T

Variant names:

• chr2-74465163-G-T
• rs369653963
• NM_006302.3:c.85C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006302.3(MOGS):​c.85C>A​(p.Arg29Arg) 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.

• 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: 0.448
• Publications: 3 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: Ambry Genetics, G2P, Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000286883 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.448 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3	c.85C>A	p.Arg29Arg	synonymous_variant	Exon 1 of 4	ENST00000448666.7	NP_006293.2
MOGS	NM_001146158.2	c.-59+151C>A		intron_variant	Intron 1 of 4		NP_001139630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7	c.85C>A	p.Arg29Arg	synonymous_variant	Exon 1 of 4	1	NM_006302.3	ENSP00000410992.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1378472 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680504

African (AFR) AF: 0.00 AC: 0 AN: 30062

American (AMR) AF: 0.00 AC: 0 AN: 35396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24764

East Asian (EAS) AF: 0.00 AC: 0 AN: 34828

South Asian (SAS) AF: 0.00 AC: 0 AN: 78756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077284

Other (OTH) AF: 0.00 AC: 0 AN: 57552

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.45
PromoterAI		-0.076	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs369653963; hg19: chr2-74692290;