Variant chr14-46957434-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3 linkuse as main transcript	c.2029G>T	p.Val677Phe	missense_variant	9/17	ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8 linkuse as main transcript	c.2029G>T	p.Val677Phe	missense_variant	9/17	1	NM_001113498.3	P1	Q7Z553-3
MDGA2	ENST00000357362.7 linkuse as main transcript	c.1135G>T	p.Val379Phe	missense_variant	9/17	5			Q7Z553-2
MDGA2	ENST00000557238.5 linkuse as main transcript	c.*407G>T		3_prime_UTR_variant, NMD_transcript_variant	9/14	5

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

GnomAD3 exomes

AF:

0.0960

AC:

23935

AN:

249318

Hom.:

2567

AF XY:

0.0843

AC XY:

11400

AN XY:

135260

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 SAS exome

AF:

0.0948

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

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.0390

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.0912

Gnomad4 FIN exome

AF:

0.0478

Gnomad4 NFE exome

AF:

0.0252

Gnomad4 OTH exome

AF:

0.0620

GnomAD4 genome

AF:

0.118

AC:

17899

AN:

152074

Hom.:

2000

Cov.:

AF XY:

0.121

AC XY:

8990

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.117

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.0269

Gnomad4 OTH

AF:

0.0951

Alfa

AF:

0.0462

Hom.:

1036

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

D;D;D

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;.;N

MutationTaster

Benign

0.90

P;P;P;P

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.037

Sift

Benign

0.051

T;D;.

Sift4G

Benign

0.44

.;T;.

Polyphen

0.21

.;.;B

Vest4

0.15

MPC

0.25

ClinPred

0.0085

GERP RS

4.3

Varity_R

0.14

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over