14-46934974-C-G

Variant names:

• chr14-46934974-C-G
• rs7151262
• NM_001113498.3:c.2090-14814G>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.2090-14814G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,366 control chromosomes in the GnomAD database, including 25,745 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 0.58 (25745 hom., cov: 29)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 6 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 (SAS) allele frequency at 95% confidence interval = 0.578 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.2090-14814G>C		intron	N/A	NP_001106970.4
	MDGA2	NM_182830.4		c.1196-14814G>C		intron	N/A	NP_878250.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.2090-14814G>C		intron	N/A	ENSP00000382178.4
	MDGA2	ENST00000357362.7	TSL:5	c.1196-14814G>C		intron	N/A	ENSP00000349925.3
	MDGA2	ENST00000557238.5	TSL:5	n.*468-14814G>C		intron	N/A	ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87800 AN: 151250 Hom.: 25703 Cov.: 29

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.581 AC: 87901 AN: 151366 Hom.: 25745 Cov.: 29 AF XY: 0.584 AC XY: 43134 AN XY: 73920

African (AFR) AF: 0.575 AC: 23673 AN: 41198

American (AMR) AF: 0.580 AC: 8802 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2005 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2052 AN: 5116

South Asian (SAS) AF: 0.594 AC: 2855 AN: 4808

European-Finnish (FIN) AF: 0.690 AC: 7212 AN: 10452

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39539 AN: 67846

Other (OTH) AF: 0.550 AC: 1147 AN: 2086

Alfa AF: 0.576 Hom.: 3001

Bravo AF: 0.573

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.25
DANN	Benign	0.44
PhyloP100		-1.2
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: rs7151262; hg19: chr14-47404177;