rs17118552

Variant names:

• chr14-47405354-A-G
• rs17118552
• NM_001113498.3:c.281-103804T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001113498.3(MDGA2):​c.281-103804T>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
• Publications: 4 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=-0.6).
• 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 rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.281-103804T>C		intron_variant	Intron 1 of 16	ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.281-103804T>C		intron_variant	Intron 1 of 9		XP_011534824.1
MDGA2	XM_047431051.1	c.281-103804T>C		intron_variant	Intron 1 of 7		XP_047287007.1
MDGA2	XM_017021061.3	c.281-103804T>C		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.281-103804T>C		intron_variant	Intron 1 of 16	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000557238.5	n.-614-103804T>C		intron_variant	Intron 1 of 13	5		ENSP00000452593.1

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

African (AFR) AF: 0.0880 AC: 3654 AN: 41546

American (AMR) AF: 0.0347 AC: 531 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0555 AC: 268 AN: 4828

European-Finnish (FIN) AF: 0.0514 AC: 545 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3075 AN: 67988

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0461 Hom.: 583

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
PhyloP100		0.27
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: rs17118552; hg19: chr14-47874557;