rs1959813

Variant names:

• chr14-46926157-C-T
• rs1959813
• NM_001113498.3:c.2090-5997G>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.2090-5997G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,954 control chromosomes in the GnomAD database, including 31,056 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 0.63 (31056 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.2090-5997G>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.2090-5997G>A		intron_variant	Intron 9 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000357362.7	c.1196-5997G>A		intron_variant	Intron 9 of 16	5		ENSP00000349925.3
MDGA2	ENST00000557238.5	n.*468-5997G>A		intron_variant	Intron 9 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96020 AN: 151836 Hom.: 30990 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.633 AC: 96150 AN: 151954 Hom.: 31056 Cov.: 32 AF XY: 0.634 AC XY: 47049 AN XY: 74268

African (AFR) AF: 0.763 AC: 31629 AN: 41444

American (AMR) AF: 0.599 AC: 9131 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2073 AN: 5150

South Asian (SAS) AF: 0.599 AC: 2886 AN: 4820

European-Finnish (FIN) AF: 0.687 AC: 7257 AN: 10564

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39288 AN: 67930

Other (OTH) AF: 0.591 AC: 1250 AN: 2114

Alfa AF: 0.607 Hom.: 4760

Bravo AF: 0.633

Asia WGS AF: 0.578 AC: 2012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.9
DANN	Benign	0.47
PhyloP100		0.17
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: rs1959813; hg19: chr14-47395360;