2-134243103-A-G

Position:

• chr2-134243103-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371457.1(MGAT5):​c.-142-11159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 151,792 control chromosomes in the GnomAD database, including 54,000 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54000 hom., cov: 29)
• Consequence: MGAT5 NM_001371457.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

MGAT5 (HGNC:7049): (alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase) The protein encoded by this gene belongs to the glycosyltransferase family. It catalyzes the addition of beta-1,6-N-acetylglucosamine to the alpha-linked mannose of biantennary N-linked oligosaccharides present on the newly synthesized glycoproteins. It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. Alterations of the oligosaccharides on cell surface glycoproteins cause significant changes in the adhesive or migratory behavior of a cell. Increase in the activity of this enzyme has been correlated with the progression of invasive malignancies. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT5	NM_001371457.1	c.-142-11159A>G		intron_variant
MGAT5	XM_005263669.6	c.-139-11162A>G		intron_variant
MGAT5	XM_006712534.4	c.-359-6947A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT5	ENST00000409645.5	c.-142-11159A>G		intron_variant		5		P1
MGAT5	ENST00000468758.1	n.310-9992A>G		intron_variant, non_coding_transcript_variant		5
MGAT5	ENST00000481801.5	n.310-11162A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127672 AN: 151674 Hom.: 53945 Cov.: 29

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.827

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.842 AC: 127791 AN: 151792 Hom.: 54000 Cov.: 29 AF XY: 0.841 AC XY: 62385 AN XY: 74154

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.819

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.826

Alfa AF: 0.840 Hom.: 10088

Bravo AF: 0.838

Asia WGS AF: 0.832 AC: 2891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.76

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: rs1257187; hg19: chr2-135000674;