chr14-47355318-C-T

Variant names:

• chr14-47355318-C-T
• rs2416054
• NM_001113498.3:c.281-53768G>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.281-53768G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,958 control chromosomes in the GnomAD database, including 2,355 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 0.17 (2355 hom., cov: 32)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	NM_001113498.3	MANE Select	c.281-53768G>A		intron	N/A	NP_001106970.4	Q7Z553-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.281-53768G>A		intron	N/A	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000557238.5	TSL:5	n.-614-53768G>A		intron	N/A	ENSP00000452593.1	G3V5Z1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25262 AN: 151840 Hom.: 2350 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.166 AC: 25290 AN: 151958 Hom.: 2355 Cov.: 32 AF XY: 0.163 AC XY: 12083 AN XY: 74234

African (AFR) AF: 0.184 AC: 7610 AN: 41458

American (AMR) AF: 0.131 AC: 1998 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2235 AN: 5126

South Asian (SAS) AF: 0.145 AC: 701 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1070 AN: 10518

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10921 AN: 67974

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.149 Hom.: 3088

Bravo AF: 0.171

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.44
PhyloP100		-1.8
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: rs2416054; hg19: chr14-47824521;