14-47196799-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.595+21222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,906 control chromosomes in the GnomAD database, including 13,595 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 0.41 (13595 hom., cov: 31)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.595+21222A>G		intron_variant		ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.595+21222A>G		intron_variant		1	NM_001113498.3	P1
MDGA2	ENST00000357362.7	c.-300+21222A>G		intron_variant		5
MDGA2	ENST00000482848.7	c.-300+21222A>G		intron_variant, NMD_transcript_variant		2
MDGA2	ENST00000557238.5	c.-300+21222A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62815 AN: 151788 Hom.: 13565 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.414 AC: 62875 AN: 151906 Hom.: 13595 Cov.: 31 AF XY: 0.405 AC XY: 30063 AN XY: 74252

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.428

Alfa AF: 0.391 Hom.: 8417

Bravo AF: 0.419

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.1
Dann	Benign	0.70

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: rs8021814; hg19: chr14-47666002;