rs17118552

Positions:

• chr14-47405354-A-G

Variant summary

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

The NM_001113498.3(MDGA2):​c.281-103804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 152,230 control chromosomes in the GnomAD database, including 248 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 0.054 (248 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.281-103804T>C		intron_variant		ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.281-103804T>C		intron_variant			XP_011534824.1
MDGA2	XM_017021061.3	c.281-103804T>C		intron_variant			XP_016876550.1
MDGA2	XM_047431051.1	c.281-103804T>C		intron_variant			XP_047287007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.281-103804T>C		intron_variant		1	NM_001113498.3	ENSP00000382178	P1
MDGA2	ENST00000557238.5	c.-614-103804T>C		intron_variant, NMD_transcript_variant		5		ENSP00000452593

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8279 AN: 152112 Hom.: 249 Cov.: 32

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0512

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

GnomAD4 genome AF: 0.0544 AC: 8280 AN: 152230 Hom.: 248 Cov.: 32 AF XY: 0.0551 AC XY: 4098 AN XY: 74428

Gnomad4 AFR AF: 0.0880

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0555

Gnomad4 FIN AF: 0.0514

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0455 Hom.: 166

Bravo AF: 0.0532

Asia WGS AF: 0.0280 AC: 98 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.3
DANN	Benign	0.71

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: rs17118552; hg19: chr14-47874557;