14-46962396-A-T

Variant names:

• chr14-46962396-A-T
• rs10484196
• NM_001113498.3:c.1820-4753T>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.1820-4753T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,002 control chromosomes in the GnomAD database, including 2,013 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 0.12 (2013 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 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.1820-4753T>A		intron	N/A	NP_001106970.4	Q7Z553-3
	MDGA2	NM_182830.4		c.926-4753T>A		intron	N/A	NP_878250.2	Q7Z553-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.1820-4753T>A		intron	N/A	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000357362.7	TSL:5	c.926-4753T>A		intron	N/A	ENSP00000349925.3	Q7Z553-2
	MDGA2	ENST00000557238.5	TSL:5	n.*198-4753T>A		intron	N/A	ENSP00000452593.1	G3V5Z1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17850 AN: 151882 Hom.: 1989 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0929

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

GnomAD4 genome AF: 0.118 AC: 17929 AN: 152002 Hom.: 2013 Cov.: 32 AF XY: 0.121 AC XY: 9010 AN XY: 74316

African (AFR) AF: 0.268 AC: 11088 AN: 41404

American (AMR) AF: 0.201 AC: 3067 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.118 AC: 608 AN: 5154

South Asian (SAS) AF: 0.100 AC: 483 AN: 4816

European-Finnish (FIN) AF: 0.0492 AC: 521 AN: 10598

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0269 AC: 1831 AN: 67970

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0870 Hom.: 141

Bravo AF: 0.138

Asia WGS AF: 0.153 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.35
PhyloP100		-0.14
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: rs10484196; hg19: chr14-47431599;