rs121909292

Positions:

• chr2-74461835-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_006302.3(MOGS):​c.1954T>C​(p.Phe652Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 8.14

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924
• PP5: Variant 2-74461835-A-G is Pathogenic according to our data. Variant chr2-74461835-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 8194.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-74461835-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOGS	NM_006302.3	c.1954T>C	p.Phe652Leu	missense_variant	4/4	ENST00000448666.7	NP_006293.2
MOGS	NM_001146158.2	c.1636T>C	p.Phe546Leu	missense_variant	5/5		NP_001139630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7	c.1954T>C	p.Phe652Leu	missense_variant	4/4	1	NM_006302.3	ENSP00000410992	P1

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;D;.;D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.6	M;M;.;.;.
MutationTaster	Benign	1.0	A;A;A
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.5	.;D;.;.;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0090	.;D;.;.;D
Sift4G	Uncertain	0.015	.;D;.;.;D
Polyphen		0.99	D;D;.;.;.
Vest4		0.94, 0.93
MutPred		0.82		Loss of catalytic residue at F652 (P = 0.0363);Loss of catalytic residue at F652 (P = 0.0363);.;.;.;
MVP		0.84
MPC		0.88
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.47
gMVP		0.78

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: rs121909292; hg19: chr2-74688962;