rs121909291

Variant names:

• chr2-74462332-C-G
• rs121909291
• NM_006302.3:c.1457G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-74462332-C-G
• chr2-74462332-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_006302.3(MOGS):​c.1457G>C​(p.Arg486Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOGS NM_006302.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.06

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985
• PP5: Variant 2-74462332-C-G is Pathogenic according to our data. Variant chr2-74462332-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 8193.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-74462332-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3	c.1457G>C	p.Arg486Thr	missense_variant	Exon 4 of 4	ENST00000448666.7	NP_006293.2
MOGS	NM_001146158.2	c.1139G>C	p.Arg380Thr	missense_variant	Exon 5 of 5		NP_001139630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7	c.1457G>C	p.Arg486Thr	missense_variant	Exon 4 of 4	1	NM_006302.3	ENSP00000410992.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

MOGS-congenital disorder of glycosylation Pathogenic:1

Jun 01, 2000

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;T;.;.;.;.
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	.;D;.;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	3.6	H;H;.;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.0	.;D;.;.;D;.
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	.;D;.;.;D;.
Sift4G	Pathogenic	0.0	.;D;.;.;D;.
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.96, 0.94
MutPred		0.97		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;.;.;
MVP		0.87
MPC		1.1
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.98

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

Other links and lift over

dbSNP: rs121909291; hg19: chr2-74689459;