rs1990577

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_012301.4(MAGI2):c.966-42T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,432,782 control chromosomes in the GnomAD database, including 223,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24049 hom., cov: 30)

Exomes 𝑓: 0.55 ( 199226 hom. )

Consequence

MAGI2
NM_012301.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.03

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 7-78489882-A-C is Benign according to our data. Variant chr7-78489882-A-C is described in ClinVar as Benign. ClinVar VariationId is 1237001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.966-42T>G		intron_variant	Intron 5 of 21	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.966-42T>G		intron_variant	Intron 5 of 21	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

84585

AN:

148040

Hom.:

24030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.576

GnomAD2 exomes

AF:

0.606

AC:

133969

AN:

221162

AF XY:

0.601

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.774

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.584

GnomAD4 exome

AF:

0.553

AC:

710326

AN:

1284628

Hom.:

199226

Cov.:

AF XY:

0.554

AC XY:

358118

AN XY:

646316

show subpopulations

African (AFR)

AF:

0.526

AC:

14873

AN:

28286

American (AMR)

AF:

0.725

AC:

26575

AN:

36668

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

12868

AN:

23558

East Asian (EAS)

AF:

0.761

AC:

29526

AN:

38794

South Asian (SAS)

AF:

0.647

AC:

50121

AN:

77438

European-Finnish (FIN)

AF:

0.576

AC:

30200

AN:

52414

Middle Eastern (MID)

AF:

0.486

AC:

2565

AN:

5282

European-Non Finnish (NFE)

AF:

0.531

AC:

513723

AN:

968214

Other (OTH)

AF:

0.554

AC:

29875

AN:

53974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

14985

29970

44954

59939

74924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14228

28456

42684

56912

71140

<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:

0.571

AC:

84643

AN:

148154

Hom.:

24049

Cov.:

AF XY:

0.577

AC XY:

41681

AN XY:

72180

show subpopulations

African (AFR)

AF:

0.548

AC:

21864

AN:

39882

American (AMR)

AF:

0.655

AC:

9686

AN:

14788

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

1842

AN:

3434

East Asian (EAS)

AF:

0.775

AC:

3954

AN:

5102

South Asian (SAS)

AF:

0.668

AC:

3134

AN:

4690

European-Finnish (FIN)

AF:

0.594

AC:

6003

AN:

10098

Middle Eastern (MID)

AF:

0.500

AC:

141

AN:

282

European-Non Finnish (NFE)

AF:

0.544

AC:

36382

AN:

66926

Other (OTH)

AF:

0.572

AC:

1177

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1822

3644

5466

7288

9110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.532

Hom.:

13201

Bravo

AF:

0.561

Asia WGS

AF:

0.682

AC:

2371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 20, 2019

GeneDx

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

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 85% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 79. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

2.0

PromoterAI

-0.0044

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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