rs10484197

chr14-46950540-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113498.3(MDGA2):c.2089+6834G>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 151,912 control chromosomes in the GnomAD database, including 2,003 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 (2003 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.2089+6834G>A		intron_variant		ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.2089+6834G>A		intron_variant		1	NM_001113498.3	P1
MDGA2	ENST00000357362.7	c.1195+6834G>A		intron_variant		5
MDGA2	ENST00000557238.5	c.*467+6834G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17794 AN: 151794 Hom.: 1982 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.118 AC: 17868 AN: 151912 Hom.: 2003 Cov.: 32 AF XY: 0.121 AC XY: 8973 AN XY: 74246

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0999

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0954

Alfa AF: 0.0866 Hom.: 138

Bravo AF: 0.137

Asia WGS AF: 0.148 AC: 514 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.39
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs10484197; hg19: chr14-47419743;