rs2416009

Variant names:

• chr14-46935815-A-T
• rs2416009
• NM_001113498.3:c.2090-15655T>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.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
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	NM_001113498.3	MANE Select	c.2090-15655T>A		intron	N/A	NP_001106970.4	Q7Z553-3
	MDGA2	NM_182830.4		c.1196-15655T>A		intron	N/A	NP_878250.2	Q7Z553-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.2090-15655T>A		intron	N/A	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000357362.7	TSL:5	c.1196-15655T>A		intron	N/A	ENSP00000349925.3	Q7Z553-2
	MDGA2	ENST00000557238.5	TSL:5	n.*468-15655T>A		intron	N/A	ENSP00000452593.1	G3V5Z1

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

African (AFR) AF: 0.580 AC: 23989 AN: 41362

American (AMR) AF: 0.580 AC: 8836 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1999 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2055 AN: 5120

South Asian (SAS) AF: 0.595 AC: 2865 AN: 4816

European-Finnish (FIN) AF: 0.688 AC: 7215 AN: 10482

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39556 AN: 67858

Other (OTH) AF: 0.551 AC: 1160 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.27
PhyloP100		-0.23
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: rs2416009; hg19: chr14-47405018;