chr14-47638437-T-C

Variant names:

• chr14-47638437-T-C
• rs1958628
• NM_001113498.3:c.280+36080A>G

Variant summary

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

The NM_001113498.3(MDGA2):​c.280+36080A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,960 control chromosomes in the GnomAD database, including 13,255 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 0.40 (13255 hom., cov: 31)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.280+36080A>G		intron_variant	Intron 1 of 16	ENST00000399232.8	NP_001106970.4
MDGA2	XM_011536522.4	c.280+36080A>G		intron_variant	Intron 1 of 9		XP_011534824.1
MDGA2	XM_047431051.1	c.280+36080A>G		intron_variant	Intron 1 of 7		XP_047287007.1
MDGA2	XM_017021061.3	c.280+36080A>G		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.280+36080A>G		intron_variant	Intron 1 of 16	1	NM_001113498.3	ENSP00000382178.4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60784 AN: 151842 Hom.: 13258 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.400 AC: 60779 AN: 151960 Hom.: 13255 Cov.: 31 AF XY: 0.387 AC XY: 28760 AN XY: 74296

African (AFR) AF: 0.302 AC: 12527 AN: 41446

American (AMR) AF: 0.348 AC: 5318 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3468

East Asian (EAS) AF: 0.0887 AC: 457 AN: 5154

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4810

European-Finnish (FIN) AF: 0.361 AC: 3817 AN: 10582

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34087 AN: 67924

Other (OTH) AF: 0.429 AC: 904 AN: 2106

Alfa AF: 0.465 Hom.: 56481

Bravo AF: 0.394

Asia WGS AF: 0.160 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.18
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: rs1958628; hg19: chr14-48107640;