NM_006302.3:c.2112C>T

Variant names:

• chr2-74461677-G-A
• rs561758565
• NM_006302.3:c.2112C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006302.3(MOGS):​c.2112C>T​(p.Pro704Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,614,214 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00081 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (35 hom.)
• Consequence: MOGS NM_006302.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00900
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 2-74461677-G-A is Benign according to our data. Variant chr2-74461677-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 465840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.009 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000814 (124/152340) while in subpopulation SAS AF = 0.0248 (120/4832). AF 95% confidence interval is 0.0212. There are 4 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGS	NM_006302.3	MANE Select	c.2112C>T	p.Pro704Pro	synonymous	Exon 4 of 4	NP_006293.2	A0A384MDR6
	MOGS	NM_001146158.2		c.1794C>T	p.Pro598Pro	synonymous	Exon 5 of 5	NP_001139630.1	Q13724-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGS	ENST00000448666.7	TSL:1 MANE Select	c.2112C>T	p.Pro704Pro	synonymous	Exon 4 of 4	ENSP00000410992.3	Q13724-1
	MOGS	ENST00000452063.7	TSL:1	c.1794C>T	p.Pro598Pro	synonymous	Exon 5 of 5	ENSP00000388201.2	Q13724-2
	MOGS	ENST00000649854.1		c.1743C>T	p.Pro581Pro	synonymous	Exon 3 of 3	ENSP00000496797.1	A0A3B3IRK6

Frequencies

GnomAD3 genomes AF: 0.000801 AC: 122 AN: 152222 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00283 AC: 705 AN: 249480 AF XY: 0.00379

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000991

GnomAD4 exome AF: 0.00133 AC: 1950 AN: 1461874 Hom.: 35 Cov.: 31 AF XY: 0.00195 AC XY: 1415 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0213 AC: 1839 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1112002

Other (OTH) AF: 0.00121 AC: 73 AN: 60394

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152340 Hom.: 4 Cov.: 33 AF XY: 0.00114 AC XY: 85 AN XY: 74496

African (AFR) AF: 0.0000481 AC: 2 AN: 41576

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0248 AC: 120 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000277 Hom.: 0

Bravo AF: 0.000128

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	MOGS-congenital disorder of glycosylation (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.6
DANN	Benign	0.86
PhyloP100		0.0090
Mutation Taster		=98/2	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: rs561758565; hg19: chr2-74688804;