dbSNP rs12590500: MDGA2:p.Val677Phe (chr14-46957434-C-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.2029G>T(p.Val677Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 1,613,874 control chromosomes in the GnomAD database, including 6,663 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 2000 hom., cov: 32)

Exomes 𝑓: 0.048 ( 4663 hom. )

Consequence

MDGA2
NM_001113498.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

Publications

16 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047100484).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 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.2029G>T	p.Val677Phe	missense	Exon 9 of 17	NP_001106970.4	Q7Z553-3
	MDGA2	NM_182830.4		c.1135G>T	p.Val379Phe	missense	Exon 9 of 17	NP_878250.2	Q7Z553-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.2029G>T	p.Val677Phe	missense	Exon 9 of 17	ENSP00000382178.4	Q7Z553-3
MDGA2	ENST00000357362.7	TSL:5	c.1135G>T	p.Val379Phe	missense	Exon 9 of 17	ENSP00000349925.3	Q7Z553-2
MDGA2	ENST00000557238.5	TSL:5	n.*407G>T		non_coding_transcript_exon	Exon 9 of 14	ENSP00000452593.1	G3V5Z1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17825

AN:

151956

Hom.:

1979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0937

GnomAD2 exomes

AF:

0.0960

AC:

23935

AN:

249318

AF XY:

0.0843

show subpopulations

Gnomad AFR exome

AF:

0.278

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.0375

Gnomad EAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.0474

Gnomad NFE exome

AF:

0.0258

Gnomad OTH exome

AF:

0.0719

GnomAD4 exome

AF:

0.0479

AC:

70048

AN:

1461800

Hom.:

4663

Cov.:

AF XY:

0.0474

AC XY:

34457

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.280

AC:

9375

AN:

33478

American (AMR)

AF:

0.279

AC:

12465

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0390

AC:

1019

AN:

26134

East Asian (EAS)

AF:

0.119

AC:

4720

AN:

39686

South Asian (SAS)

AF:

0.0912

AC:

7867

AN:

86256

European-Finnish (FIN)

AF:

0.0478

AC:

2551

AN:

53414

Middle Eastern (MID)

AF:

0.0456

AC:

263

AN:

5768

European-Non Finnish (NFE)

AF:

0.0252

AC:

28042

AN:

1111956

Other (OTH)

AF:

0.0620

AC:

3746

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3425

6850

10275

13700

17125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1446

2892

4338

5784

7230

<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:

0.118

AC:

17899

AN:

152074

Hom.:

2000

Cov.:

AF XY:

0.121

AC XY:

8990

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.267

AC:

11067

AN:

41434

American (AMR)

AF:

0.200

AC:

3059

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

127

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

607

AN:

5166

South Asian (SAS)

AF:

0.100

AC:

484

AN:

4818

European-Finnish (FIN)

AF:

0.0488

AC:

517

AN:

10596

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0269

AC:

1832

AN:

68006

Other (OTH)

AF:

0.0951

AC:

201

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

720

1439

2159

2878

3598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0582

Hom.:

3187

Bravo

AF:

0.138

TwinsUK

AF:

0.0262

AC:

ALSPAC

AF:

0.0226

AC:

ESP6500AA

AF:

0.253

AC:

941

ESP6500EA

AF:

0.0233

AC:

191

ExAC

AF:

0.0893

AC:

10792

Asia WGS

AF:

0.150

AC:

519

AN:

3478

EpiCase

AF:

0.0248

EpiControl

AF:

0.0212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

1.4

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

REVEL

Benign

0.037

Sift

Benign

0.051

Sift4G

Benign

0.44

Polyphen

0.21

Vest4

0.15

MPC

0.25

ClinPred

0.0085

GERP RS

4.3

Varity_R

0.14

gMVP

0.60

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over