rs10483569

chr14-47516079-T-C

Variant summary

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

The NM_001113498.3(MDGA2):c.280+158438A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,196 control chromosomes in the GnomAD database, including 993 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 0.11 (993 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.280+158438A>G		intron_variant		ENST00000399232.8
MDGA2	XM_011536522.4	c.280+158438A>G		intron_variant
MDGA2	XM_017021061.3	c.280+158438A>G		intron_variant
MDGA2	XM_047431051.1	c.280+158438A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.280+158438A>G		intron_variant		1	NM_001113498.3	P1
MDGA2	ENST00000557238.5	c.-615+110260A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16470 AN: 152078 Hom.: 995 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.108 AC: 16475 AN: 152196 Hom.: 993 Cov.: 32 AF XY: 0.104 AC XY: 7741 AN XY: 74434

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.103

Alfa AF: 0.110 Hom.: 550

Bravo AF: 0.114

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.2
Dann	Benign	0.76

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: rs10483569; hg19: chr14-47985282;