chr2-74461320-G-T

Variant names:

• chr2-74461320-G-T
• rs751765295
• NM_006302.3:c.2469C>A

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.2469C>A​(p.His823Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H823H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOGS NM_006302.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• 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: Ambry Genetics, G2P, Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

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=0.19584543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3	c.2469C>A	p.His823Gln	missense_variant	Exon 4 of 4	ENST00000448666.7	NP_006293.2
MOGS	NM_001146158.2	c.2151C>A	p.His717Gln	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.2469C>A	p.His823Gln	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.20
DANN	Benign	0.82
DEOGEN2	Benign	0.018	T;T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.70	.;T;.;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;.;.;.
PhyloP100		-2.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.71	.;N;.;.;N
REVEL	Benign	0.071
Sift	Benign	0.17	.;T;.;.;T
Sift4G	Uncertain	0.060	.;T;.;.;D
Polyphen		0.0	B;B;.;.;.
Vest4		0.054, 0.051
MutPred		0.66		Loss of disorder (P = 0.1757);Loss of disorder (P = 0.1757);.;.;.;
MVP		0.18
MPC		0.24
ClinPred		0.072	T
GERP RS		-9.6
Varity_R		0.024
gMVP		0.74
Mutation Taster		=86/14	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: rs751765295; hg19: chr2-74688447;