14-46898413-C-T

Variant names:

• chr14-46898413-C-T
• rs3007105
• NM_001113498.3:c.2239-16192G>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.2239-16192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,724 control chromosomes in the GnomAD database, including 13,256 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 0.39 (13256 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 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.2239-16192G>A		intron	N/A	NP_001106970.4
	MDGA2	NM_182830.4		c.1345-16192G>A		intron	N/A	NP_878250.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.2239-16192G>A		intron	N/A	ENSP00000382178.4
	MDGA2	ENST00000357362.7	TSL:5	c.1345-16192G>A		intron	N/A	ENSP00000349925.3
	MDGA2	ENST00000555521.1	TSL:3	n.164-16192G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59890 AN: 151606 Hom.: 13249 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.395 AC: 59901 AN: 151724 Hom.: 13256 Cov.: 32 AF XY: 0.399 AC XY: 29556 AN XY: 74154

African (AFR) AF: 0.212 AC: 8777 AN: 41418

American (AMR) AF: 0.612 AC: 9323 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1561 AN: 3462

East Asian (EAS) AF: 0.634 AC: 3261 AN: 5144

South Asian (SAS) AF: 0.422 AC: 2030 AN: 4808

European-Finnish (FIN) AF: 0.344 AC: 3625 AN: 10548

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.439 AC: 29795 AN: 67806

Other (OTH) AF: 0.446 AC: 938 AN: 2102

Alfa AF: 0.422 Hom.: 2780

Bravo AF: 0.410

Asia WGS AF: 0.448 AC: 1555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.51
PhyloP100		0.0040
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: rs3007105; hg19: chr14-47367616;