7-78019354-G-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.4329C>G(p.Pro1443Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,508,894 control chromosomes in the GnomAD database, including 48,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7847 hom., cov: 30)

Exomes 𝑓: 0.23 ( 41145 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.794

Publications

17 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=-0.71).

BP6

Variant 7-78019354-G-C is Benign according to our data. Variant chr7-78019354-G-C is described in ClinVar as [Benign]. Clinvar id is 95514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.794 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.4329C>G	p.Pro1443Pro	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.4329C>G	p.Pro1443Pro	synonymous_variant	Exon 22 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

44596

AN:

150236

Hom.:

7836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.276

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.308

AC:

33794

AN:

109592

AF XY:

0.301

show subpopulations

Gnomad AFR exome

AF:

0.411

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.639

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.227

AC:

308509

AN:

1358552

Hom.:

41145

Cov.:

AF XY:

0.230

AC XY:

154144

AN XY:

671056

show subpopulations

African (AFR)

AF:

0.427

AC:

12381

AN:

29008

American (AMR)

AF:

0.399

AC:

12757

AN:

31992

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

6778

AN:

24390

East Asian (EAS)

AF:

0.652

AC:

20794

AN:

31902

South Asian (SAS)

AF:

0.354

AC:

26952

AN:

76138

European-Finnish (FIN)

AF:

0.248

AC:

8368

AN:

33708

Middle Eastern (MID)

AF:

0.236

AC:

1203

AN:

5098

European-Non Finnish (NFE)

AF:

0.191

AC:

204480

AN:

1069700

Other (OTH)

AF:

0.261

AC:

14796

AN:

56616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

12151

24302

36452

48603

60754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.297

AC:

44650

AN:

150342

Hom.:

7847

Cov.:

AF XY:

0.304

AC XY:

22293

AN XY:

73418

show subpopulations

African (AFR)

AF:

0.422

AC:

17408

AN:

41212

American (AMR)

AF:

0.320

AC:

4848

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

959

AN:

3456

East Asian (EAS)

AF:

0.639

AC:

3205

AN:

5012

South Asian (SAS)

AF:

0.373

AC:

1789

AN:

4802

European-Finnish (FIN)

AF:

0.274

AC:

2745

AN:

10002

Middle Eastern (MID)

AF:

0.266

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.191

AC:

12877

AN:

67414

Other (OTH)

AF:

0.264

AC:

551

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

1477

2954

4430

5907

7384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.154

Hom.:

436

Bravo

AF:

0.309

Asia WGS

AF:

0.499

AC:

1729

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 22, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported. -

Mar 01, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 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

- -

Nephrotic syndrome 15

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

-0.71

CADD

Benign

5.0

(source)

DANN

Benign

0.68

PhyloP100

-0.79

Mutation Taster

=100/0

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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7-78019354-G-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