Genetic Variant MDGA2:c.281-3748C>A (chr14-47305298-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001113498.3(MDGA2):c.281-3748C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,978 control chromosomes in the GnomAD database, including 4,534 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 ( 4534 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MDGA2
NM_001113498.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.17

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MDGA2	NM_001113498.3	MANE Select	c.281-3748C>A	intron	N/A	NP_001106970.4
MDGA2	NM_182830.4		c.-609-3748C>A	intron	N/A	NP_878250.2
MDGA2	NR_103766.2		n.150-3748C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.281-3748C>A	intron	N/A	ENSP00000382178.4
MDGA2	ENST00000472499.2	TSL:5	n.111C>A	non_coding_transcript_exon	Exon 3 of 5
MDGA2	ENST00000357362.7	TSL:5	c.-614-3748C>A	intron	N/A	ENSP00000349925.3

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33125

AN:

151858

Hom.:

4519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.0925

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0950

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.181

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.218

AC:

33163

AN:

151978

Hom.:

4534

Cov.:

AF XY:

0.212

AC XY:

15716

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.369

AC:

15309

AN:

41440

American (AMR)

AF:

0.148

AC:

2255

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0925

AC:

320

AN:

3460

East Asian (EAS)

AF:

0.443

AC:

2278

AN:

5140

South Asian (SAS)

AF:

0.115

AC:

554

AN:

4814

European-Finnish (FIN)

AF:

0.0950

AC:

1006

AN:

10586

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10973

AN:

67958

Other (OTH)

AF:

0.187

AC:

395

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1239

2478

3716

4955

6194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.191

Hom.:

525

Bravo

AF:

0.231

Asia WGS

AF:

0.279

AC:

971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

1.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over