NM_001113498.3:c.280+89561T>C

Variant names:

• chr14-47584956-A-G
• rs4143912
• NM_001113498.3:c.280+89561T>C

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+89561T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,492 control chromosomes in the GnomAD database, including 14,421 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 0.41 (14421 hom., cov: 31)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.280+89561T>C		intron_variant	Intron 1 of 16	ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.280+89561T>C		intron_variant	Intron 1 of 9		XP_011534824.1
MDGA2	XM_047431051.1	c.280+89561T>C		intron_variant	Intron 1 of 7		XP_047287007.1
MDGA2	XM_017021061.3	c.280+89561T>C		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+89561T>C		intron_variant	Intron 1 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-615+41383T>C		intron_variant	Intron 1 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62657 AN: 151374 Hom.: 14404 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.414 AC: 62719 AN: 151492 Hom.: 14421 Cov.: 31 AF XY: 0.424 AC XY: 31400 AN XY: 73974

African (AFR) AF: 0.303 AC: 12526 AN: 41388

American (AMR) AF: 0.534 AC: 8083 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1444 AN: 3460

East Asian (EAS) AF: 0.931 AC: 4761 AN: 5114

South Asian (SAS) AF: 0.715 AC: 3436 AN: 4808

European-Finnish (FIN) AF: 0.407 AC: 4289 AN: 10536

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26733 AN: 67722

Other (OTH) AF: 0.402 AC: 848 AN: 2108

Alfa AF: 0.411 Hom.: 35615

Bravo AF: 0.418

Asia WGS AF: 0.785 AC: 2720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.73
PhyloP100		0.32
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: rs4143912; hg19: chr14-48054159;