rs8019096

Positions:

• chr14-47494268-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.280+180249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,068 control chromosomes in the GnomAD database, including 42,315 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 0.74 (42315 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.280+180249G>A		intron_variant		ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.280+180249G>A		intron_variant			XP_011534824.1
MDGA2	XM_047431051.1	c.280+180249G>A		intron_variant			XP_047287007.1
MDGA2	XM_017021061.3	c.280+180249G>A		intron_variant			XP_016876550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.280+180249G>A		intron_variant		1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-615+132071G>A		intron_variant		5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112703 AN: 151950 Hom.: 42283 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.742 AC: 112786 AN: 152068 Hom.: 42315 Cov.: 32 AF XY: 0.749 AC XY: 55687 AN XY: 74314

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.723

Alfa AF: 0.740 Hom.: 7927

Bravo AF: 0.737

Asia WGS AF: 0.915 AC: 3175 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.48

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: rs8019096; hg19: chr14-47963471;