rs12433343

Variant names:

• chr14-47078541-A-G
• rs12433343
• NM_001113498.3:c.1196-16963T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.99).
• 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 rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.1196-16963T>C		intron_variant	Intron 6 of 16	ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.1196-16963T>C		intron_variant	Intron 6 of 16	1	NM_001113498.3	ENSP00000382178.4

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

African (AFR) AF: 0.169 AC: 7005 AN: 41486

American (AMR) AF: 0.289 AC: 4416 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3470

East Asian (EAS) AF: 0.117 AC: 605 AN: 5160

South Asian (SAS) AF: 0.176 AC: 847 AN: 4818

European-Finnish (FIN) AF: 0.175 AC: 1857 AN: 10608

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13571 AN: 67972

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.203 Hom.: 10420

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
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12433343; hg19: chr14-47547744;