14-47515816-G-T

Variant names:

• chr14-47515816-G-T
• rs10147486
• NM_001113498.3:c.280+158701C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113498.3(MDGA2):​c.280+158701C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,064 control chromosomes in the GnomAD database, including 5,491 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 0.25 (5491 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 2 publications found

Genes affected

MDGA2 (HGNC:19835): (MAM domain containing glycosylphosphatidylinositol anchor 2) Predicted to be involved in regulation of presynapse assembly; regulation of synaptic membrane adhesion; and spinal cord motor neuron differentiation. Predicted to act upstream of or within neuron migration and pattern specification process. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in GABA-ergic synapse and glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	NM_001113498.3	MANE Select	c.280+158701C>A		intron	N/A	NP_001106970.4	Q7Z553-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.280+158701C>A		intron	N/A	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000557238.5	TSL:5	n.-615+110523C>A		intron	N/A	ENSP00000452593.1	G3V5Z1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37530 AN: 151946 Hom.: 5484 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.247 AC: 37538 AN: 152064 Hom.: 5491 Cov.: 32 AF XY: 0.256 AC XY: 19011 AN XY: 74302

African (AFR) AF: 0.108 AC: 4469 AN: 41516

American (AMR) AF: 0.374 AC: 5705 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5168

South Asian (SAS) AF: 0.474 AC: 2278 AN: 4810

European-Finnish (FIN) AF: 0.342 AC: 3623 AN: 10580

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18595 AN: 67954

Other (OTH) AF: 0.242 AC: 511 AN: 2110

Alfa AF: 0.264 Hom.: 7273

Bravo AF: 0.241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.59
PhyloP100		-0.081
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10147486; hg19: chr14-47985019;