14-47546779-A-C

Position:

• chr14-47546779-A-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+127738T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,994 control chromosomes in the GnomAD database, including 8,497 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 (8497 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.280+127738T>G		intron_variant		ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.280+127738T>G		intron_variant			XP_011534824.1
MDGA2	XM_047431051.1	c.280+127738T>G		intron_variant			XP_047287007.1
MDGA2	XM_017021061.3	c.280+127738T>G		intron_variant			XP_016876550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.280+127738T>G		intron_variant		1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-615+79560T>G		intron_variant		5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48004 AN: 151874 Hom.: 8484 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.316 AC: 48031 AN: 151994 Hom.: 8497 Cov.: 32 AF XY: 0.321 AC XY: 23812 AN XY: 74290

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.337

Alfa AF: 0.340 Hom.: 5371

Bravo AF: 0.301

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.063
DANN	Benign	0.67

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: rs1160351; hg19: chr14-48015982;