rs10484189

Positions:

• chr14-47259924-G-A

Variant summary

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

The NM_001113498.3(MDGA2):​c.420+41487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 152,072 control chromosomes in the GnomAD database, including 171 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 0.031 (171 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729

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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.420+41487C>T		intron_variant		ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.420+41487C>T		intron_variant		1	NM_001113498.3	P1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4737 AN: 151952 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00762

Gnomad OTH AF: 0.0235

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

GnomAD4 genome AF: 0.0312 AC: 4742 AN: 152072 Hom.: 171 Cov.: 32 AF XY: 0.0340 AC XY: 2530 AN XY: 74350

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.0182

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0709

Gnomad4 FIN AF: 0.0422

Gnomad4 NFE AF: 0.00762

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0138 Hom.: 89

Bravo AF: 0.0308

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs10484189; hg19: chr14-47729127;