rs8019096

Variant names:

• chr14-47494268-C-T
• rs8019096
• NM_001113498.3:c.280+180249G>A

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+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
• Publications: 2 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=-0.96).
• 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 rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.280+180249G>A		intron_variant	Intron 1 of 16	ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.280+180249G>A		intron_variant	Intron 1 of 9		XP_011534824.1
MDGA2	XM_047431051.1	c.280+180249G>A		intron_variant	Intron 1 of 7		XP_047287007.1
MDGA2	XM_017021061.3	c.280+180249G>A		intron_variant	Intron 1 of 7		XP_016876550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.280+180249G>A		intron_variant	Intron 1 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-615+132071G>A		intron_variant	Intron 1 of 13	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

African (AFR) AF: 0.667 AC: 27662 AN: 41450

American (AMR) AF: 0.788 AC: 12022 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5170 AN: 5176

South Asian (SAS) AF: 0.844 AC: 4068 AN: 4820

European-Finnish (FIN) AF: 0.813 AC: 8602 AN: 10586

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50481 AN: 67992

Other (OTH) AF: 0.723 AC: 1527 AN: 2112

Alfa AF: 0.738 Hom.: 8096

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
PhyloP100		-2.1
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: rs8019096; hg19: chr14-47963471;