rs145722885

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012301.4(MAGI2):c.2213G>A(p.Arg738Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,880 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 11 hom. )

Consequence

MAGI2
NM_012301.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.16

Publications

9 publications found

Variant links:

Genes affected

MAGI2 (HGNC:18957): (membrane associated guanylate kinase, WW and PDZ domain containing 2) The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. [provided by RefSeq, Jul 2008]

MAGI2 Gene-Disease associations (from GenCC):

nephrotic syndrome 15
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: G2P
epilepsy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MAGI2 links:

LOC124901684 (HGNC:):

LOC124901684 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00938037).

BP6

Variant 7-78194930-C-T is Benign according to our data. Variant chr7-78194930-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012301.4. 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
	MAGI2	NM_012301.4	MANE Select	c.2213G>A	p.Arg738Gln	missense	Exon 12 of 22	NP_036433.2
	MAGI2	NM_001301128.2		c.2213G>A	p.Arg738Gln	missense	Exon 12 of 21	NP_001288057.1	Q86UL8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.2213G>A	p.Arg738Gln	missense	Exon 12 of 22	ENSP00000346151.4	Q86UL8-1
MAGI2	ENST00000419488.5	TSL:1	c.2213G>A	p.Arg738Gln	missense	Exon 12 of 21	ENSP00000405766.1	Q86UL8-2
MAGI2	ENST00000519748.5	TSL:1	c.1040G>A	p.Arg347Gln	missense	Exon 8 of 16	ENSP00000486774.1	A0A0D9SFP3

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00198

AC:

496

AN:

250932

AF XY:

0.00223

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000986

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00229

AC:

3344

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1738

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33464

American (AMR)

AF:

0.00101

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00191

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39682

South Asian (SAS)

AF:

0.00409

AC:

353

AN:

86220

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.0109

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00240

AC:

2663

AN:

1111886

Other (OTH)

AF:

0.00240

AC:

145

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

164

328

491

655

819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.00158

AC:

241

AN:

152274

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41554

American (AMR)

AF:

0.00150

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00237

AC:

161

AN:

68020

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00212

Hom.:

Bravo

AF:

0.00174

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00204

AC:

248

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00317

EpiControl

AF:

0.00291

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

MAGI2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.065

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0094

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

PhyloP100

2.2

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.93

REVEL

Benign

0.077

Sift

Benign

0.043

Sift4G

Benign

0.24

Polyphen

0.96

Vest4

0.46

MVP

0.14

MPC

0.36

ClinPred

0.017

GERP RS

5.8

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.13

gMVP

0.33

Mutation Taster

=100/0

polymorphism

(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

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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