14-49621035-T-C

Position:

• chr14-49621035-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT2	NM_002408.4	c.-234T>C		5_prime_UTR_variant	1/1	ENST00000305386.4	NP_002399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT2	ENST00000305386.4	c.-234T>C		5_prime_UTR_variant	1/1		NM_002408.4	ENSP00000307423	P1
	ENST00000555043.1	n.2249A>G		non_coding_transcript_exon_variant	2/2	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

GnomAD3 exomes AF: 0.427 AC: 55013 AN: 128872 Hom.: 13306 AF XY: 0.440 AC XY: 31005 AN XY: 70466

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 SAS exome AF: 0.482

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

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.575

Gnomad4 EAS exome AF: 0.0931

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.460

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

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.414

Alfa AF: 0.467 Hom.: 6606

Bravo AF: 0.363

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

MGAT2-congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital disorder of glycosylation Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.87
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

Publications

LitVar

Other links and lift over

dbSNP: rs7519; hg19: chr14-50087753; COSMIC: COSV53566057; COSMIC: COSV53566057;