14-49621035-T-C

Variant names:

• chr14-49621035-T-C
• rs7519
• NM_002408.4:c.-234T>C

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.-234T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 715,734 control chromosomes in the GnomAD database, including 84,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (14689 hom., cov: 33)
  • Exomes 𝑓: 0.48 (69838 hom.)
• Consequence: MGAT2 NM_002408.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.787
• Publications: 8 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 14-49621035-T-C is Benign according to our data. Variant chr14-49621035-T-C is described in ClinVar as Benign. ClinVar VariationId is 313249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGAT2	NM_002408.4	MANE Select	c.-234T>C		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.-234T>C		5_prime_UTR	Exon 1 of 1	ENSP00000307423.2	Q10469
	ENSG00000258377	ENST00000555043.2	TSL:2	n.2249A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60531 AN: 151988 Hom.: 14688 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.412

GnomAD2 exomes AF: 0.427 AC: 55013 AN: 128872 AF XY: 0.440

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.570

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.568

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.478 AC: 269668 AN: 563628 Hom.: 69838 Cov.: 5 AF XY: 0.483 AC XY: 146966 AN XY: 304224

African (AFR) AF: 0.143 AC: 2291 AN: 15996

American (AMR) AF: 0.284 AC: 9862 AN: 34688

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 11548 AN: 20082

East Asian (EAS) AF: 0.0931 AC: 2993 AN: 32148

South Asian (SAS) AF: 0.482 AC: 30330 AN: 62976

European-Finnish (FIN) AF: 0.575 AC: 19055 AN: 33166

Middle Eastern (MID) AF: 0.480 AC: 1788 AN: 3726

European-Non Finnish (NFE) AF: 0.538 AC: 177528 AN: 329840

Other (OTH) AF: 0.460 AC: 14273 AN: 31006

GnomAD4 genome AF: 0.398 AC: 60541 AN: 152106 Hom.: 14689 Cov.: 33 AF XY: 0.399 AC XY: 29703 AN XY: 74360

African (AFR) AF: 0.143 AC: 5937 AN: 41538

American (AMR) AF: 0.347 AC: 5314 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.126 AC: 647 AN: 5150

South Asian (SAS) AF: 0.478 AC: 2305 AN: 4822

European-Finnish (FIN) AF: 0.589 AC: 6230 AN: 10584

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36597 AN: 67922

Other (OTH) AF: 0.414 AC: 876 AN: 2114

Alfa AF: 0.463 Hom.: 7823

Bravo AF: 0.363

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.79
PromoterAI		0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs7519; hg19: chr14-50087753; COSMIC: COSV53566057; COSMIC: COSV53566057;