2-134427820-T-C

Position:

• chr2-134427820-T-C

Variant summary

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

The NM_002410.5(MGAT5):​c.1795-545T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,142 control chromosomes in the GnomAD database, including 6,848 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 0.26 (6848 hom., cov: 33)
• Consequence: MGAT5 NM_002410.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGAT5	NM_002410.5	c.1795-545T>C		intron_variant		ENST00000281923.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGAT5	ENST00000281923.4	c.1795-545T>C		intron_variant		1	NM_002410.5	P1
MGAT5	ENST00000409645.5	c.1795-545T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39967 AN: 152024 Hom.: 6825 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.263 AC: 40035 AN: 152142 Hom.: 6848 Cov.: 33 AF XY: 0.263 AC XY: 19561 AN XY: 74382

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.271

Alfa AF: 0.172 Hom.: 4380

Bravo AF: 0.282

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.24

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: rs16830611; hg19: chr2-135185391;