rs2416065

Positions:

• chr14-47406161-C-A
• chr14-47406161-C-G
• chr14-47406161-C-T

Variant summary

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

The NM_001113498.3(MDGA2):​c.281-104611G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 151,944 control chromosomes in the GnomAD database, including 39,546 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 0.72 (39546 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.281-104611G>T		intron_variant		ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.281-104611G>T		intron_variant			XP_011534824.1
MDGA2	XM_017021061.3	c.281-104611G>T		intron_variant			XP_016876550.1
MDGA2	XM_047431051.1	c.281-104611G>T		intron_variant			XP_047287007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.281-104611G>T		intron_variant		1	NM_001113498.3	ENSP00000382178	P1
MDGA2	ENST00000557238.5	c.-614-104611G>T		intron_variant, NMD_transcript_variant		5		ENSP00000452593

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108752 AN: 151826 Hom.: 39520 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.716 AC: 108831 AN: 151944 Hom.: 39546 Cov.: 32 AF XY: 0.723 AC XY: 53715 AN XY: 74272

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.696

Alfa AF: 0.646 Hom.: 1933

Bravo AF: 0.713

Asia WGS AF: 0.903 AC: 3107 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.46
DANN	Benign	0.23

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: rs2416065; hg19: chr14-47875364;