rs2066310

Variant names:

• chr14-46952197-C-T
• rs2066310
• NM_001113498.3:c.2089+5177G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113498.3(MDGA2):​c.2089+5177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 151,262 control chromosomes in the GnomAD database, including 511 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 0.059 (511 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.2089+5177G>A		intron_variant	Intron 9 of 16	ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.2089+5177G>A		intron_variant	Intron 9 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000357362.7	c.1195+5177G>A		intron_variant	Intron 9 of 16	5		ENSP00000349925.3
MDGA2	ENST00000557238.5	n.*467+5177G>A		intron_variant	Intron 9 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 8955 AN: 151144 Hom.: 506 Cov.: 32

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0559

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

GnomAD4 genome AF: 0.0594 AC: 8981 AN: 151262 Hom.: 511 Cov.: 32 AF XY: 0.0631 AC XY: 4656 AN XY: 73794

African (AFR) AF: 0.0683 AC: 2817 AN: 41222

American (AMR) AF: 0.181 AC: 2741 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3468

East Asian (EAS) AF: 0.0966 AC: 495 AN: 5126

South Asian (SAS) AF: 0.0833 AC: 400 AN: 4802

European-Finnish (FIN) AF: 0.0454 AC: 472 AN: 10386

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1823 AN: 67806

Other (OTH) AF: 0.0572 AC: 120 AN: 2098

Alfa AF: 0.0512 Hom.: 42

Bravo AF: 0.0722

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.37
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2066310; hg19: chr14-47421400;