14-46950540-C-T

Variant names:

• chr14-46950540-C-T
• rs10484197
• NM_001113498.3:c.2089+6834G>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.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
• 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=-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 rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.2089+6834G>A		intron_variant	Intron 9 of 16	ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.2089+6834G>A		intron_variant	Intron 9 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000357362.7	c.1195+6834G>A		intron_variant	Intron 9 of 16	5		ENSP00000349925.3
MDGA2	ENST00000557238.5	n.*467+6834G>A		intron_variant	Intron 9 of 13	5		ENSP00000452593.1

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

African (AFR) AF: 0.267 AC: 11043 AN: 41430

American (AMR) AF: 0.200 AC: 3046 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3466

East Asian (EAS) AF: 0.119 AC: 612 AN: 5162

South Asian (SAS) AF: 0.0999 AC: 482 AN: 4826

European-Finnish (FIN) AF: 0.0491 AC: 520 AN: 10590

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1832 AN: 67906

Other (OTH) AF: 0.0954 AC: 201 AN: 2108

Alfa AF: 0.0924 Hom.: 163

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
PhyloP100		-1.1
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: rs10484197; hg19: chr14-47419743;