14-47099865-A-G

Variant names:

• chr14-47099865-A-G
• rs10149991
• NM_001113498.3:c.926-2742T>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.926-2742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,850 control chromosomes in the GnomAD database, including 20,993 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 0.52 (20993 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	NM_001113498.3	MANE Select	c.926-2742T>C		intron	N/A	NP_001106970.4	Q7Z553-3
	MDGA2	NM_182830.4		c.32-2742T>C		intron	N/A	NP_878250.2	Q7Z553-2
	MDGA2	NR_103766.2		n.790-2742T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.926-2742T>C		intron	N/A	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000357362.7	TSL:5	c.32-2742T>C		intron	N/A	ENSP00000349925.3	Q7Z553-2
	MDGA2	ENST00000554762.5	TSL:3	c.125-2826T>C		intron	N/A	ENSP00000450827.1	H0YJ52

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79000 AN: 151732 Hom.: 20962 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.521 AC: 79080 AN: 151850 Hom.: 20993 Cov.: 32 AF XY: 0.521 AC XY: 38627 AN XY: 74194

African (AFR) AF: 0.640 AC: 26517 AN: 41450

American (AMR) AF: 0.511 AC: 7785 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2868 AN: 5158

South Asian (SAS) AF: 0.348 AC: 1681 AN: 4826

European-Finnish (FIN) AF: 0.551 AC: 5827 AN: 10568

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.468 AC: 31732 AN: 67842

Other (OTH) AF: 0.490 AC: 1029 AN: 2098

Alfa AF: 0.513 Hom.: 3498

Bravo AF: 0.528

Asia WGS AF: 0.506 AC: 1758 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	0.38
PhyloP100		-0.41
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: rs10149991; hg19: chr14-47569068;