chr14-49620919-C-G

Variant names:

• chr14-49620919-C-G
• rs886050515
• NM_002408.4:c.-350C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002408.4(MGAT2):​c.-350C>G variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MGAT2 NM_002408.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

Genes affected

MGAT2 (HGNC:7045): (alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase) The product of this gene is a Golgi enzyme catalyzing an essential step in the conversion of oligomannose to complex N-glycans. The enzyme has the typical glycosyltransferase domains: a short N-terminal cytoplasmic domain, a hydrophobic non-cleavable signal-anchor domain, and a C-terminal catalytic domain. Mutations in this gene may lead to carbohydrate-deficient glycoprotein syndrome, type II. The coding region of this gene is intronless. Transcript variants with a spliced 5' UTR may exist, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

MGAT2 Gene-Disease associations (from GenCC):

• MGAT2-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000258377 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002408.4. 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
	MGAT2	NM_002408.4	MANE Select	c.-350C>G		5_prime_UTR	Exon 1 of 1	NP_002399.1	Q10469

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT2	ENST00000305386.4	TSL:6 MANE Select	c.-350C>G		5_prime_UTR	Exon 1 of 1	ENSP00000307423.2	Q10469
	ENSG00000258377	ENST00000555043.2	TSL:2	n.2365G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 549148 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 297326

African (AFR) AF: 0.00 AC: 0 AN: 15734

American (AMR) AF: 0.00 AC: 0 AN: 34624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19964

East Asian (EAS) AF: 0.00 AC: 0 AN: 32062

South Asian (SAS) AF: 0.00 AC: 0 AN: 62740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3900

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 316430

Other (OTH) AF: 0.00 AC: 0 AN: 30540

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	MGAT2-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		1.8
PromoterAI		0.25	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs886050515; hg19: chr14-50087637;