NM_001113498.3:c.281-91724G>C

Variant names:

• chr14-47393274-C-G
• rs10483573
• NM_001113498.3:c.281-91724G>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.281-91724G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,438 control chromosomes in the GnomAD database, including 5,519 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 0.26 (5519 hom., cov: 31)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.281-91724G>C		intron_variant	Intron 1 of 16	ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.281-91724G>C		intron_variant	Intron 1 of 9		XP_011534824.1
MDGA2	XM_047431051.1	c.281-91724G>C		intron_variant	Intron 1 of 7		XP_047287007.1
MDGA2	XM_017021061.3	c.281-91724G>C		intron_variant	Intron 1 of 7		XP_016876550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.281-91724G>C		intron_variant	Intron 1 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-614-91724G>C		intron_variant	Intron 1 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39626 AN: 151320 Hom.: 5517 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.262 AC: 39644 AN: 151438 Hom.: 5519 Cov.: 31 AF XY: 0.255 AC XY: 18892 AN XY: 73988

African (AFR) AF: 0.305 AC: 12612 AN: 41366

American (AMR) AF: 0.224 AC: 3407 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1131 AN: 3458

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5166

South Asian (SAS) AF: 0.157 AC: 755 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2288 AN: 10336

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18443 AN: 67786

Other (OTH) AF: 0.291 AC: 613 AN: 2110

Alfa AF: 0.135 Hom.: 219

Bravo AF: 0.263

Asia WGS AF: 0.0880 AC: 306 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.082
DANN	Benign	0.31
PhyloP100		-1.1
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: rs10483573; hg19: chr14-47862477;