Variant 14-46957483-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001113498.3(MDGA2):c.1980G>C(p.Gln660His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000807 in 1,614,084 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 19 hom. )

Consequence

MDGA2
NM_001113498.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.319

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026649833).

BP6

Variant 14-46957483-C-G is Benign according to our data. Variant chr14-46957483-C-G is described in ClinVar as [Benign]. Clinvar id is 729728.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000907 (138/152212) while in subpopulation EAS AF= 0.0227 (117/5158). AF 95% confidence interval is 0.0193. There are 2 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3 linkuse as main transcript	c.1980G>C	p.Gln660His	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.1980G>C	p.Gln660His	missense_variant	9/17	1	NM_001113498.3	P1	Q7Z553-3
MDGA2	ENST00000357362.7 linkuse as main transcript	c.1086G>C	p.Gln362His	missense_variant	9/17	5			Q7Z553-2
MDGA2	ENST00000557238.5 linkuse as main transcript	c.*358G>C		3_prime_UTR_variant, NMD_transcript_variant	9/14	5

Frequencies

GnomAD3 genomes

AF:

0.000901

AC:

137

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0224

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00204

AC:

510

AN:

249480

Hom.:

AF XY:

0.00177

AC XY:

240

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0273

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000796

AC:

1164

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000727

AC XY:

529

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0265

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.000907

AC:

138

AN:

152212

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0227

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000867

Hom.:

Bravo

AF:

0.00122

ESP6500AA

AF:

0.00105

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00189

AC:

228

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

.;.;T

Eigen

Benign

0.097

Eigen_PC

Benign

0.049

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

.;.;L

MutationTaster

Benign

0.86

D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.12

Sift

Benign

0.11

T;T;.

Sift4G

Benign

0.067

.;T;.

Polyphen

0.91

.;.;P

Vest4

0.26

MutPred

0.31

.;.;Gain of catalytic residue at F588 (P = 0.0196);

MVP

0.26

MPC

0.17

ClinPred

0.031

GERP RS

2.1

Varity_R

0.069

gMVP

0.50

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