2-134257776-A-G

Position:

• chr2-134257776-A-G

Variant summary

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

The NM_002410.5(MGAT5):​c.241+3132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 150,464 control chromosomes in the GnomAD database, including 42,144 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 0.75 (42144 hom., cov: 26)
• Consequence: MGAT5 NM_002410.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT5	NM_002410.5	c.241+3132A>G		intron_variant		ENST00000281923.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT5	ENST00000281923.4	c.241+3132A>G		intron_variant		1	NM_002410.5	P1
MGAT5	ENST00000409645.5	c.241+3132A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 112337 AN: 150352 Hom.: 42116 Cov.: 26

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.747 AC: 112417 AN: 150464 Hom.: 42144 Cov.: 26 AF XY: 0.748 AC XY: 54767 AN XY: 73212

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.717

Alfa AF: 0.749 Hom.: 19469

Bravo AF: 0.744

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.48

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: rs1257220; hg19: chr2-135015347;