Genetic Variant MAGI2:c.966-42T>A (chr7-78489882-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012301.4(MAGI2):c.966-42T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000536 in 1,435,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000094 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

MAGI2
NM_012301.4 intron

Scores

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0000945

AC:

AN:

148174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000677

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000747

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000588

AC:

AN:

221162

AF XY:

0.0000250

show subpopulations

Gnomad AFR exome

AF:

0.000396

Gnomad AMR exome

AF:

0.0000745

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000387

Gnomad OTH exome

AF:

0.000196

GnomAD4 exome

AF:

0.0000489

AC:

AN:

1287658

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

647800

show subpopulations

African (AFR)

AF:

0.000282

AC:

AN:

28346

American (AMR)

AF:

0.0000545

AC:

AN:

36686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23588

East Asian (EAS)

AF:

0.00

AC:

AN:

38810

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52462

Middle Eastern (MID)

AF:

0.000756

AC:

AN:

5288

European-Non Finnish (NFE)

AF:

0.0000402

AC:

AN:

970852

Other (OTH)

AF:

0.000166

AC:

AN:

54092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000944

AC:

AN:

148288

Hom.:

Cov.:

AF XY:

0.0000969

AC XY:

AN XY:

72272

show subpopulations

African (AFR)

AF:

0.000175

AC:

AN:

39952

American (AMR)

AF:

0.0000676

AC:

AN:

14798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.000213

AC:

AN:

4694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000747

AC:

AN:

66946

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

13201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

2.0

PromoterAI

-0.062

Neutral

(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

Computational scores

Splicing

Publications

Other links and lift over