14-49621529-G-T

Variant names:

• chr14-49621529-G-T
• rs2228449
• NM_002408.4:c.261G>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_002408.4(MGAT2):​c.261G>T​(p.Leu87Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00304 in 1,612,886 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (70 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (70 hom.)
• Consequence: MGAT2 NM_002408.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.62
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics

ENSG00000258377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 14-49621529-G-T is Benign according to our data. Variant chr14-49621529-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 313255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT2	NM_002408.4	MANE Select	c.261G>T	p.Leu87Leu	synonymous	Exon 1 of 1	NP_002399.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT2	ENST00000305386.4	TSL:6 MANE Select	c.261G>T	p.Leu87Leu	synonymous	Exon 1 of 1	ENSP00000307423.2
	ENSG00000258377	ENST00000555043.2	TSL:2	n.1952C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2463 AN: 152190 Hom.: 70 Cov.: 33

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00410 AC: 1015 AN: 247630 AF XY: 0.00302

Gnomad AFR exome AF: 0.0562

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000126

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00167 AC: 2435 AN: 1460578 Hom.: 70 Cov.: 32 AF XY: 0.00141 AC XY: 1027 AN XY: 726414

African (AFR) AF: 0.0591 AC: 1978 AN: 33464

American (AMR) AF: 0.00324 AC: 145 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52792

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5764

European-Non Finnish (NFE) AF: 0.0000693 AC: 77 AN: 1111448

Other (OTH) AF: 0.00343 AC: 207 AN: 60332

GnomAD4 genome AF: 0.0162 AC: 2468 AN: 152308 Hom.: 70 Cov.: 33 AF XY: 0.0158 AC XY: 1174 AN XY: 74468

African (AFR) AF: 0.0557 AC: 2316 AN: 41556

American (AMR) AF: 0.00725 AC: 111 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.00779 Hom.: 16

Bravo AF: 0.0188

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	MGAT2-congenital disorder of glycosylation (2)
-	-	1	Congenital disorder of glycosylation (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs2228449; hg19: chr14-50088247;