rs9323124

chr14-46996974-T-A

Variant summary

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

The NM_001113498.3(MDGA2):c.1819+38037A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 388,572 control chromosomes in the GnomAD database, including 8,843 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 0.22 (3999 hom., cov: 32)
  • Exomes 𝑓: 0.19 (4844 hom.)
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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]

RPA2P1 (HGNC:19676): (replication protein A2 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.1819+38037A>T		intron_variant		ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.1819+38037A>T		intron_variant		1	NM_001113498.3	P1
RPA2P1	ENST00000556557.1	n.521T>A		non_coding_transcript_exon_variant	1/1
MDGA2	ENST00000357362.7	c.925+38037A>T		intron_variant		5
MDGA2	ENST00000557238.5	c.*197+38037A>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33813 AN: 151964 Hom.: 4002 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.186 AC: 43927 AN: 236488 Hom.: 4844 Cov.: 0 AF XY: 0.183 AC XY: 25353 AN XY: 138760

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.0307

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.222 AC: 33828 AN: 152084 Hom.: 3999 Cov.: 32 AF XY: 0.224 AC XY: 16612 AN XY: 74326

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0354

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.190

Alfa AF: 0.236 Hom.: 2506

Bravo AF: 0.211

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.80
Dann	Benign	0.83

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: rs9323124; hg19: chr14-47466177; COSMIC: COSV62095148;