14-46950443-A-G

Variant names:

• chr14-46950443-A-G
• rs10484198
• NM_001113498.3:c.2089+6931T>C

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+6931T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 152,100 control chromosomes in the GnomAD database, including 503 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 0.058 (503 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.861
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.2089+6931T>C		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+6931T>C		intron_variant	Intron 9 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000357362.7	c.1195+6931T>C		intron_variant	Intron 9 of 16	5		ENSP00000349925.3
MDGA2	ENST00000557238.5	n.*467+6931T>C		intron_variant	Intron 9 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8818 AN: 151982 Hom.: 498 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0556

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

GnomAD4 genome AF: 0.0581 AC: 8843 AN: 152100 Hom.: 503 Cov.: 32 AF XY: 0.0618 AC XY: 4597 AN XY: 74340

African (AFR) AF: 0.0654 AC: 2717 AN: 41514

American (AMR) AF: 0.180 AC: 2737 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3472

East Asian (EAS) AF: 0.0965 AC: 498 AN: 5162

South Asian (SAS) AF: 0.0833 AC: 402 AN: 4828

European-Finnish (FIN) AF: 0.0444 AC: 472 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0263 AC: 1784 AN: 67940

Other (OTH) AF: 0.0569 AC: 120 AN: 2110

Alfa AF: 0.0382 Hom.: 246

Bravo AF: 0.0709

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.64
PhyloP100		0.86
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: rs10484198; hg19: chr14-47419646;