Variant 14-47131743-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001113498.3(MDGA2):c.896T>C(p.Met299Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00357 in 1,580,262 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 85 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 81 hom. )

Consequence

MDGA2
NM_001113498.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.51

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004794866).

BP6

Variant 14-47131743-A-G is Benign according to our data. Variant chr14-47131743-A-G is described in ClinVar as [Benign]. Clinvar id is 710031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0644 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.896T>C	p.Met299Thr	missense_variant	5/17	ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8 linkuse as main transcript	c.896T>C	p.Met299Thr	missense_variant	5/17	1	NM_001113498.3	P1	Q7Z553-3

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2889

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00577

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00458

AC:

1137

AN:

248250

Hom.:

AF XY:

0.00356

AC XY:

480

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.0647

Gnomad AMR exome

AF:

0.00317

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00193

AC:

2758

AN:

1428158

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1185

AN XY:

709136

show subpopulations

Gnomad4 AFR exome

AF:

0.0680

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.000195

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.00473

GnomAD4 genome

AF:

0.0190

AC:

2887

AN:

152104

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1411

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0665

Gnomad4 AMR

AF:

0.00576

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.0211

ESP6500AA

AF:

0.0601

AC:

224

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.00562

AC:

679

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

.;.;T

Eigen

Benign

-0.062

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

T;D;T

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

.;.;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.48

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.69

T;D;.

Sift4G

Uncertain

0.016

.;D;.

Polyphen

0.0070

.;.;B

Vest4

0.69

MVP

0.16

ClinPred

0.018

GERP RS

5.3

Varity_R

0.16

gMVP

0.37

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over