NM_012301.4:c.4269G>C

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.4269G>C(p.Pro1423Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,128,038 control chromosomes in the GnomAD database, including 30,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6856 hom., cov: 29)

Exomes 𝑓: 0.21 ( 23572 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

Publications

6 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=-0.74).

BP6

Variant 7-78019414-C-G is Benign according to our data. Variant chr7-78019414-C-G is described in ClinVar as [Benign]. Clinvar id is 95513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.4269G>C	p.Pro1423Pro	synonymous_variant	Exon 22 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.4269G>C	p.Pro1423Pro	synonymous_variant	Exon 22 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

41184

AN:

145556

Hom.:

6851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.265

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.253

GnomAD2 exomes

AF:

0.349

AC:

259

AN:

742

AF XY:

0.362

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.569

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.205

AC:

201647

AN:

982416

Hom.:

23572

Cov.:

AF XY:

0.205

AC XY:

95060

AN XY:

462686

show subpopulations

African (AFR)

AF:

0.420

AC:

8306

AN:

19754

American (AMR)

AF:

0.373

AC:

1947

AN:

5224

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

2821

AN:

10178

East Asian (EAS)

AF:

0.593

AC:

11074

AN:

18670

South Asian (SAS)

AF:

0.338

AC:

6312

AN:

18690

European-Finnish (FIN)

AF:

0.226

AC:

2964

AN:

13136

Middle Eastern (MID)

AF:

0.249

AC:

593

AN:

2378

European-Non Finnish (NFE)

AF:

0.185

AC:

158436

AN:

857672

Other (OTH)

AF:

0.250

AC:

9194

AN:

36714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

8807

17615

26422

35230

44037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.283

AC:

41214

AN:

145622

Hom.:

6856

Cov.:

AF XY:

0.288

AC XY:

20434

AN XY:

70856

show subpopulations

African (AFR)

AF:

0.404

AC:

16384

AN:

40588

American (AMR)

AF:

0.309

AC:

4575

AN:

14782

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

928

AN:

3400

East Asian (EAS)

AF:

0.560

AC:

2749

AN:

4906

South Asian (SAS)

AF:

0.353

AC:

1670

AN:

4736

European-Finnish (FIN)

AF:

0.243

AC:

2028

AN:

8344

Middle Eastern (MID)

AF:

0.257

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.184

AC:

12097

AN:

65640

Other (OTH)

AF:

0.255

AC:

523

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

1371

2742

4112

5483

6854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.238

Hom.:

619

Bravo

AF:

0.295

Asia WGS

AF:

0.438

AC:

1421

AN:

3254

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 01, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 22, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.9

(source)

DANN

Benign

0.82

PhyloP100

-1.1

Mutation Taster

=95/5

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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NM_012301.4:c.4269G>C

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