rs11627056

Positions:

• chr14-46985783-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.1820-28140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,844 control chromosomes in the GnomAD database, including 8,195 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 0.29 (8195 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.1820-28140C>T		intron_variant		ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.1820-28140C>T		intron_variant		1	NM_001113498.3	P1
MDGA2	ENST00000357362.7	c.926-28140C>T		intron_variant		5
MDGA2	ENST00000557238.5	c.*198-28140C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44220 AN: 151726 Hom.: 8197 Cov.: 32

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.291 AC: 44215 AN: 151844 Hom.: 8195 Cov.: 32 AF XY: 0.285 AC XY: 21165 AN XY: 74214

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.0556

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.315

Alfa AF: 0.381 Hom.: 11053

Bravo AF: 0.281

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.56

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: rs11627056; hg19: chr14-47454986;