chr14-49622036-T-G

Position:

chr14-49622036-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002408.4(MGAT2):c.768T>G(p.Leu256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00098 in 1,613,998 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 13 hom. )

Consequence

MGAT2
NM_002408.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.219

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 14-49622036-T-G is Benign according to our data. Variant chr14-49622036-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 461189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.219 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0011 (168/152108) while in subpopulation EAS AF= 0.0182 (94/5170). AF 95% confidence interval is 0.0152. There are 2 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGAT2	NM_002408.4 linkuse as main transcript	c.768T>G	p.Leu256=	synonymous_variant	1/1	ENST00000305386.4	NP_002399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGAT2	ENST00000305386.4 linkuse as main transcript	c.768T>G	p.Leu256=	synonymous_variant	1/1		NM_002408.4	ENSP00000307423	P1
	ENST00000555043.1 linkuse as main transcript	n.1445A>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

170

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00232

AC:

584

AN:

251464

Hom.:

AF XY:

0.00221

AC XY:

301

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.0214

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00554

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000967

AC:

1414

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000965

AC XY:

702

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0210

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.00599

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152108

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

118

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0182

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00481

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000319

Hom.:

Bravo

AF:

0.00117

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MGAT2-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 05, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 22, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over