14-47536598-T-C

Position:

• chr14-47536598-T-C

Variant summary

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

The NM_001113498.3(MDGA2):​c.280+137919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,184 control chromosomes in the GnomAD database, including 5,826 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 0.26 (5826 hom., cov: 33)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.280+137919A>G		intron_variant		ENST00000399232.8
MDGA2	XM_011536522.4	c.280+137919A>G		intron_variant
MDGA2	XM_017021061.3	c.280+137919A>G		intron_variant
MDGA2	XM_047431051.1	c.280+137919A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.280+137919A>G		intron_variant		1	NM_001113498.3	P1
MDGA2	ENST00000557238.5	c.-615+89741A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39935 AN: 152066 Hom.: 5813 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.263 AC: 39974 AN: 152184 Hom.: 5826 Cov.: 33 AF XY: 0.272 AC XY: 20215 AN XY: 74380

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.242

Alfa AF: 0.252 Hom.: 619

Bravo AF: 0.259

Asia WGS AF: 0.435 AC: 1507 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	1.6
DANN	Benign	0.64

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: rs1955810; hg19: chr14-48005801;