14-47515816-G-T

Variant names:

• chr14-47515816-G-T
• rs10147486
• NM_001113498.3:c.280+158701C>A

Variant summary

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

The NM_001113498.3(MDGA2):​c.280+158701C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,064 control chromosomes in the GnomAD database, including 5,491 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 0.25 (5491 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.280+158701C>A		intron_variant	Intron 1 of 16	ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.280+158701C>A		intron_variant	Intron 1 of 9		XP_011534824.1
MDGA2	XM_047431051.1	c.280+158701C>A		intron_variant	Intron 1 of 7		XP_047287007.1
MDGA2	XM_017021061.3	c.280+158701C>A		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+158701C>A		intron_variant	Intron 1 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-615+110523C>A		intron_variant	Intron 1 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37530 AN: 151946 Hom.: 5484 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.247 AC: 37538 AN: 152064 Hom.: 5491 Cov.: 32 AF XY: 0.256 AC XY: 19011 AN XY: 74302

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.242

Alfa AF: 0.267 Hom.: 5581

Bravo AF: 0.241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10147486; hg19: chr14-47985019;