rs1009524

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012301.4(MAGI2):c.2784T>C(p.Asn928Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,607,866 control chromosomes in the GnomAD database, including 8,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 983 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7845 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.772

Publications

13 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-78160086-A-G is Benign according to our data. Variant chr7-78160086-A-G is described in ClinVar as [Benign]. Clinvar id is 129563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.772 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.2784T>C	p.Asn928Asn	synonymous_variant	Exon 16 of 22	ENST00000354212.9	NP_036433.2	Q86UL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 link	c.2784T>C	p.Asn928Asn	synonymous_variant	Exon 16 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16994

AN:

152136

Hom.:

982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.0832

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0982

Gnomad OTH

AF:

0.108

GnomAD2 exomes

AF:

0.119

AC:

29574

AN:

248480

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0982

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0999

AC:

145450

AN:

1455612

Hom.:

7845

Cov.:

AF XY:

0.0997

AC XY:

72070

AN XY:

723206

show subpopulations

African (AFR)

AF:

0.114

AC:

3798

AN:

33436

American (AMR)

AF:

0.160

AC:

7087

AN:

44186

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4095

AN:

26080

East Asian (EAS)

AF:

0.181

AC:

7175

AN:

39542

South Asian (SAS)

AF:

0.0879

AC:

7433

AN:

84598

European-Finnish (FIN)

AF:

0.129

AC:

6865

AN:

53384

Middle Eastern (MID)

AF:

0.0875

AC:

503

AN:

5750

European-Non Finnish (NFE)

AF:

0.0922

AC:

102206

AN:

1108426

Other (OTH)

AF:

0.104

AC:

6288

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7923

15846

23770

31693

39616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.112

AC:

17027

AN:

152254

Hom.:

983

Cov.:

AF XY:

0.114

AC XY:

8487

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.112

AC:

4675

AN:

41556

American (AMR)

AF:

0.138

AC:

2109

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

516

AN:

3472

East Asian (EAS)

AF:

0.171

AC:

882

AN:

5156

South Asian (SAS)

AF:

0.0841

AC:

406

AN:

4828

European-Finnish (FIN)

AF:

0.132

AC:

1398

AN:

10598

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0982

AC:

6682

AN:

68024

Other (OTH)

AF:

0.107

AC:

227

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

814

1628

2441

3255

4069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.107

Hom.:

687

Bravo

AF:

0.115

Asia WGS

AF:

0.116

AC:

401

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.099

(source)

DANN

Benign

0.53

PhyloP100

-0.77

Mutation Taster

=98/2

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

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rs1009524

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over