rs9323124

Variant names:

• chr14-46996974-T-A
• rs9323124
• NM_001113498.3:c.1819+38037A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

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.1819+38037A>T		intron	N/A	NP_001106970.4	Q7Z553-3
	MDGA2	NM_182830.4		c.925+38037A>T		intron	N/A	NP_878250.2	Q7Z553-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.1819+38037A>T		intron	N/A	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000357362.7	TSL:5	c.925+38037A>T		intron	N/A	ENSP00000349925.3	Q7Z553-2
	RPA2P1	ENST00000556557.1	TSL:6	n.521T>A		non_coding_transcript_exon	Exon 1 of 1

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

African (AFR) AF: 0.142 AC: 870 AN: 6106

American (AMR) AF: 0.165 AC: 3047 AN: 18428

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 636 AN: 5724

East Asian (EAS) AF: 0.0307 AC: 268 AN: 8716

South Asian (SAS) AF: 0.114 AC: 4404 AN: 38478

European-Finnish (FIN) AF: 0.258 AC: 3089 AN: 11970

Middle Eastern (MID) AF: 0.0724 AC: 56 AN: 774

European-Non Finnish (NFE) AF: 0.218 AC: 29556 AN: 135414

Other (OTH) AF: 0.184 AC: 2001 AN: 10878

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

African (AFR) AF: 0.195 AC: 8088 AN: 41502

American (AMR) AF: 0.201 AC: 3064 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.0354 AC: 183 AN: 5176

South Asian (SAS) AF: 0.148 AC: 712 AN: 4816

European-Finnish (FIN) AF: 0.324 AC: 3421 AN: 10566

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17253 AN: 67974

Other (OTH) AF: 0.190 AC: 403 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.83
PhyloP100		-0.49
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: rs9323124; hg19: chr14-47466177; COSMIC: COSV62095148;