dbSNP rs9323124: MDGA2:c.1819+38037A>T (chr14-46996974-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.491

Publications

6 publications found

Variant links:

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]

MDGA2 links:

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

RPA2P1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3 link	c.1819+38037A>T		intron_variant	Intron 8 of 16	ENST00000399232.8	NP_001106970.4	Q7Z553-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MDGA2	ENST00000399232.8 link	c.1819+38037A>T	intron_variant	Intron 8 of 16	1	NM_001113498.3	ENSP00000382178.4	Q7Z553-3
RPA2P1	ENST00000556557.1 link	n.521T>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
MDGA2	ENST00000357362.7 link	c.925+38037A>T	intron_variant	Intron 8 of 16	5		ENSP00000349925.3	Q7Z553-2
MDGA2	ENST00000557238.5 link	n.*197+38037A>T	intron_variant	Intron 8 of 13	5		ENSP00000452593.1	G3V5Z1

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33813

AN:

151964

Hom.:

4002

Cov.:

show subpopulations

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.:

AF XY:

0.183

AC XY:

25353

AN XY:

138760

show subpopulations

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:

AN:

774

European-Non Finnish (NFE)

AF:

0.218

AC:

29556

AN:

135414

Other (OTH)

AF:

0.184

AC:

2001

AN:

10878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

1169

2338

3507

4676

5845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33828

AN:

152084

Hom.:

3999

Cov.:

AF XY:

0.224

AC XY:

16612

AN XY:

74326

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17253

AN:

67974

Other (OTH)

AF:

0.190

AC:

403

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1341

2682

4024

5365

6706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.83

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over