2-74465183-G-C

Variant names:

• chr2-74465183-G-C
• rs753961807
• NM_006302.3:c.65C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006302.3(MOGS):​c.65C>G​(p.Ala22Gly) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOGS NM_006302.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0760251).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGS	NM_006302.3	MANE Select	c.65C>G	p.Ala22Gly	missense	Exon 1 of 4	NP_006293.2
	MOGS	NM_001146158.2		c.-59+131C>G		intron	N/A	NP_001139630.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGS	ENST00000448666.7	TSL:1 MANE Select	c.65C>G	p.Ala22Gly	missense	Exon 1 of 4	ENSP00000410992.3
	MOGS	ENST00000452063.7	TSL:1	c.-59+131C>G		intron	N/A	ENSP00000388201.2
	MOGS	ENST00000690565.1		c.65C>G	p.Ala22Gly	missense	Exon 1 of 5	ENSP00000510501.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.85
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.043
Sift	Benign	0.38	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.092
MutPred		0.19		Loss of helix (P = 0.0033)
MVP		0.25
MPC		0.25
ClinPred		0.086	T
GERP RS		1.4
PromoterAI		-0.19	Neutral
Varity_R		0.066
gMVP		0.71
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753961807; hg19: chr2-74692310;