rs2416009

Positions:

• chr14-46935815-A-T

Variant summary

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

The NM_001113498.3(MDGA2):​c.2090-15655T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,638 control chromosomes in the GnomAD database, including 25,897 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 0.58 (25897 hom., cov: 31)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.2090-15655T>A		intron_variant		ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.2090-15655T>A		intron_variant		1	NM_001113498.3	ENSP00000382178	P1
MDGA2	ENST00000357362.7	c.1196-15655T>A		intron_variant		5		ENSP00000349925
MDGA2	ENST00000557238.5	c.*468-15655T>A		intron_variant, NMD_transcript_variant		5		ENSP00000452593

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88187 AN: 151522 Hom.: 25855 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.582 AC: 88288 AN: 151638 Hom.: 25897 Cov.: 31 AF XY: 0.585 AC XY: 43313 AN XY: 74076

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.551

Alfa AF: 0.584 Hom.: 3211

Bravo AF: 0.575

Asia WGS AF: 0.557 AC: 1941 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	2.5
DANN	Benign	0.27

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: rs2416009; hg19: chr14-47405018;