14-47394632-C-T

Variant names:

• chr14-47394632-C-T
• rs7159841
• NM_001113498.3:c.281-93082G>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.281-93082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,020 control chromosomes in the GnomAD database, including 39,699 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 0.72 (39699 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 10 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 (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.281-93082G>A		intron_variant	Intron 1 of 16	ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.281-93082G>A		intron_variant	Intron 1 of 9		XP_011534824.1
MDGA2	XM_047431051.1	c.281-93082G>A		intron_variant	Intron 1 of 7		XP_047287007.1
MDGA2	XM_017021061.3	c.281-93082G>A		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.281-93082G>A		intron_variant	Intron 1 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-614-93082G>A		intron_variant	Intron 1 of 13	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109409 AN: 151900 Hom.: 39674 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.720 AC: 109488 AN: 152020 Hom.: 39699 Cov.: 32 AF XY: 0.714 AC XY: 53046 AN XY: 74296

African (AFR) AF: 0.658 AC: 27292 AN: 41458

American (AMR) AF: 0.751 AC: 11459 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2842 AN: 3470

East Asian (EAS) AF: 0.614 AC: 3175 AN: 5168

South Asian (SAS) AF: 0.542 AC: 2607 AN: 4814

European-Finnish (FIN) AF: 0.712 AC: 7516 AN: 10558

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51988 AN: 67974

Other (OTH) AF: 0.754 AC: 1594 AN: 2114

Alfa AF: 0.738 Hom.: 53010

Bravo AF: 0.723

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.5
DANN	Benign	0.32
PhyloP100		0.63
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: rs7159841; hg19: chr14-47863835;