7-78489792-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012301.4(MAGI2):c.1014G>A(p.Lys338Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,610,112 control chromosomes in the GnomAD database, including 76,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8564 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68322 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.67

Publications

19 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=-0.44).

BP6

Variant 7-78489792-C-T is Benign according to our data. Variant chr7-78489792-C-T is described in ClinVar as Benign. ClinVar VariationId is 129557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.1014G>A	p.Lys338Lys	synonymous_variant	Exon 6 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.1014G>A	p.Lys338Lys	synonymous_variant	Exon 6 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49520

AN:

151548

Hom.:

8539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.317

GnomAD2 exomes

AF:

0.288

AC:

71929

AN:

249956

AF XY:

0.291

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.298

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.303

AC:

442211

AN:

1458446

Hom.:

68322

Cov.:

AF XY:

0.303

AC XY:

219956

AN XY:

725486

show subpopulations

African (AFR)

AF:

0.437

AC:

14571

AN:

33348

American (AMR)

AF:

0.203

AC:

9061

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

8037

AN:

26044

East Asian (EAS)

AF:

0.239

AC:

9472

AN:

39650

South Asian (SAS)

AF:

0.301

AC:

25863

AN:

85836

European-Finnish (FIN)

AF:

0.289

AC:

15410

AN:

53342

Middle Eastern (MID)

AF:

0.385

AC:

2214

AN:

5754

European-Non Finnish (NFE)

AF:

0.305

AC:

338642

AN:

1109682

Other (OTH)

AF:

0.314

AC:

18941

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

14100

28199

42299

56398

70498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11156

22312

33468

44624

55780

<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:

0.327

AC:

49586

AN:

151666

Hom.:

8564

Cov.:

AF XY:

0.324

AC XY:

23974

AN XY:

74082

show subpopulations

African (AFR)

AF:

0.427

AC:

17661

AN:

41366

American (AMR)

AF:

0.257

AC:

3897

AN:

15188

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1085

AN:

3466

East Asian (EAS)

AF:

0.227

AC:

1163

AN:

5128

South Asian (SAS)

AF:

0.294

AC:

1418

AN:

4816

European-Finnish (FIN)

AF:

0.283

AC:

2973

AN:

10508

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20492

AN:

67878

Other (OTH)

AF:

0.323

AC:

682

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1685

3370

5056

6741

8426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.310

Hom.:

12366

Bravo

AF:

0.329

Asia WGS

AF:

0.290

AC:

1009

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Oct 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

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. -

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 41% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.7

PromoterAI

-0.045

Neutral

(source)

Mutation Taster

=96/4

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