rs12433343

Positions:

• chr14-47078541-A-G

Variant summary

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

The NM_001113498.3(MDGA2):​c.1196-16963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,110 control chromosomes in the GnomAD database, including 2,970 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 0.20 (2970 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.1196-16963T>C		intron_variant		ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.1196-16963T>C		intron_variant		1	NM_001113498.3	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29672 AN: 151992 Hom.: 2966 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.195 AC: 29703 AN: 152110 Hom.: 2970 Cov.: 32 AF XY: 0.196 AC XY: 14587 AN XY: 74350

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.218

Alfa AF: 0.205 Hom.: 6690

Bravo AF: 0.205

Asia WGS AF: 0.170 AC: 590 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.92
DANN	Benign	0.56

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: rs12433343; hg19: chr14-47547744;