14-47052286-T-C

Variant names:

• chr14-47052286-T-C
• rs961616
• NM_001113498.3:c.1525+8963A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113498.3(MDGA2):​c.1525+8963A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,648 control chromosomes in the GnomAD database, including 8,605 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 0.32 (8605 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.1525+8963A>G		intron_variant	Intron 7 of 16	ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.1525+8963A>G		intron_variant	Intron 7 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000357362.7	c.631+8963A>G		intron_variant	Intron 7 of 16	5		ENSP00000349925.3
MDGA2	ENST00000554762.5	c.640+8963A>G		intron_variant	Intron 3 of 3	3		ENSP00000450827.1
MDGA2	ENST00000557238.5	n.631+8963A>G		intron_variant	Intron 7 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49101 AN: 151530 Hom.: 8604 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.324 AC: 49117 AN: 151648 Hom.: 8605 Cov.: 32 AF XY: 0.324 AC XY: 24002 AN XY: 74074

African (AFR) AF: 0.196 AC: 8146 AN: 41456

American (AMR) AF: 0.306 AC: 4641 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2691 AN: 5146

South Asian (SAS) AF: 0.458 AC: 2206 AN: 4820

European-Finnish (FIN) AF: 0.385 AC: 4061 AN: 10542

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25159 AN: 67748

Other (OTH) AF: 0.323 AC: 679 AN: 2100

Alfa AF: 0.358 Hom.: 5016

Bravo AF: 0.312

Asia WGS AF: 0.415 AC: 1439 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.69
PhyloP100		0.12
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: rs961616; hg19: chr14-47521489;