rs12883384

Positions:

• chr14-46934481-A-C
• chr14-46934481-A-T

Variant summary

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

The NM_001113498.3(MDGA2):​c.2090-14321T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,926 control chromosomes in the GnomAD database, including 25,777 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 0.58 (25777 hom., cov: 31)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.2090-14321T>G		intron_variant		ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.2090-14321T>G		intron_variant		1	NM_001113498.3	ENSP00000382178	P1
MDGA2	ENST00000357362.7	c.1196-14321T>G		intron_variant		5		ENSP00000349925
MDGA2	ENST00000557238.5	c.*468-14321T>G		intron_variant, NMD_transcript_variant		5		ENSP00000452593

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87997 AN: 151806 Hom.: 25741 Cov.: 31

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.580 AC: 88091 AN: 151926 Hom.: 25777 Cov.: 31 AF XY: 0.583 AC XY: 43285 AN XY: 74274

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.551

Alfa AF: 0.568 Hom.: 42966

Bravo AF: 0.572

Asia WGS AF: 0.555 AC: 1933 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.68

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: rs12883384; hg19: chr14-47403684;