7-78019768-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_012301.4(MAGI2):c.3915G>A(p.Gln1305Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,612,638 control chromosomes in the GnomAD database, including 1,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 79 hom., cov: 30)

Exomes 𝑓: 0.036 ( 1159 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.30

Publications

5 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 7-78019768-C-T is Benign according to our data. Variant chr7-78019768-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.3 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0251 (3807/151934) while in subpopulation NFE AF = 0.0409 (2779/67902). AF 95% confidence interval is 0.0397. There are 79 homozygotes in GnomAd4. There are 1748 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 79 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.3915G>A	p.Gln1305Gln	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.3915G>A	p.Gln1305Gln	synonymous_variant	Exon 22 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3809

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00814

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0409

Gnomad OTH

AF:

0.0297

GnomAD2 exomes

AF:

0.0252

AC:

6243

AN:

247638

AF XY:

0.0256

show subpopulations

Gnomad AFR exome

AF:

0.00842

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0416

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0360

AC:

52650

AN:

1460704

Hom.:

1159

Cov.:

AF XY:

0.0355

AC XY:

25801

AN XY:

726516

show subpopulations

African (AFR)

AF:

0.00687

AC:

230

AN:

33468

American (AMR)

AF:

0.0168

AC:

751

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

543

AN:

26124

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39676

South Asian (SAS)

AF:

0.0101

AC:

875

AN:

86238

European-Finnish (FIN)

AF:

0.0116

AC:

612

AN:

52538

Middle Eastern (MID)

AF:

0.0267

AC:

154

AN:

5766

European-Non Finnish (NFE)

AF:

0.0429

AC:

47645

AN:

1111802

Other (OTH)

AF:

0.0304

AC:

1837

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

2933

5867

8800

11734

14667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1758

3516

5274

7032

8790

<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:

0.0251

AC:

3807

AN:

151934

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1748

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00812

AC:

337

AN:

41504

American (AMR)

AF:

0.0222

AC:

340

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

AN:

3462

East Asian (EAS)

AF:

0.000195

AC:

AN:

5136

South Asian (SAS)

AF:

0.00974

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0110

AC:

116

AN:

10504

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0409

AC:

2779

AN:

67902

Other (OTH)

AF:

0.0294

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

189

378

567

756

945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0357

Hom.:

167

Bravo

AF:

0.0257

EpiCase

AF:

0.0402

EpiControl

AF:

0.0457

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 30, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 29, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2012

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Apr 14, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

2.3

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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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