14-47516079-T-C

Variant names:

• chr14-47516079-T-C
• rs10483569
• NM_001113498.3:c.280+158438A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	NM_001113498.3	MANE Select	c.280+158438A>G		intron	N/A	NP_001106970.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.280+158438A>G		intron	N/A	ENSP00000382178.4
	MDGA2	ENST00000557238.5	TSL:5	n.-615+110260A>G		intron	N/A	ENSP00000452593.1

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

African (AFR) AF: 0.134 AC: 5562 AN: 41508

American (AMR) AF: 0.0890 AC: 1359 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5186

South Asian (SAS) AF: 0.0418 AC: 202 AN: 4828

European-Finnish (FIN) AF: 0.0438 AC: 465 AN: 10624

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7825 AN: 67996

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.110 Hom.: 608

Bravo AF: 0.114

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.76
PhyloP100		0.30
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: rs10483569; hg19: chr14-47985282;