rs10483573

Positions:

• chr14-47393274-C-G
• chr14-47393274-C-T

Variant summary

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

The NM_001113498.3(MDGA2):​c.281-91724G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,438 control chromosomes in the GnomAD database, including 5,519 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 (5519 hom., cov: 31)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.281-91724G>C		intron_variant		ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.281-91724G>C		intron_variant			XP_011534824.1
MDGA2	XM_047431051.1	c.281-91724G>C		intron_variant			XP_047287007.1
MDGA2	XM_017021061.3	c.281-91724G>C		intron_variant			XP_016876550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.281-91724G>C		intron_variant		1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-614-91724G>C		intron_variant		5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39626 AN: 151320 Hom.: 5517 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.262 AC: 39644 AN: 151438 Hom.: 5519 Cov.: 31 AF XY: 0.255 AC XY: 18892 AN XY: 73988

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.291

Alfa AF: 0.135 Hom.: 219

Bravo AF: 0.263

Asia WGS AF: 0.0880 AC: 306 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.082
DANN	Benign	0.31

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: rs10483573; hg19: chr14-47862477;