14-47571172-G-A

Position:

• chr14-47571172-G-A

Variant summary

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

The NM_001113498.3(MDGA2):​c.280+103345C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,284 control chromosomes in the GnomAD database, including 65,166 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 0.92 (65166 hom., cov: 33)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.280+103345C>T		intron_variant		ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.280+103345C>T		intron_variant			XP_011534824.1
MDGA2	XM_047431051.1	c.280+103345C>T		intron_variant			XP_047287007.1
MDGA2	XM_017021061.3	c.280+103345C>T		intron_variant			XP_016876550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.280+103345C>T		intron_variant		1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-615+55167C>T		intron_variant		5		ENSP00000452593.1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140616 AN: 152166 Hom.: 65115 Cov.: 33

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.924 AC: 140726 AN: 152284 Hom.: 65166 Cov.: 33 AF XY: 0.928 AC XY: 69104 AN XY: 74454

Gnomad4 AFR AF: 0.979

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.911

Alfa AF: 0.907 Hom.: 7756

Bravo AF: 0.926

Asia WGS AF: 0.982 AC: 3412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.1
DANN	Benign	0.61

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: rs7144383; hg19: chr14-48040375;